Citations

Background: Within the heterogeneous genomic landscape of multiple myeloma (MM), clonal evolution including the acquisition of risk-defining mutations and chromosomal abnormalities is a recurrent event and can be detected by fluorescence in situ hybridization (FISH). The effects of acquired abnormalities on clinical outcomes have not been well defined. We previously reported that patients who acquired 17p deletion [del(17p)] during the course of their disease had a significantly reduced overall survival (OS) by 38 months compared to patients who did not acquire del17p (Lakshman et al 2019). Similarly, while de novo gain of the long arm of chromosome 1 (1q22 gain) is a known high-risk aberration associated with significantly shorter OS and progression-free survival (PFS) in MM, the prognostic significance of acquired 1q22 gain has not been described. The primary objective of this study was to analyze factors predictive for acquired 1q22 gain and determine its impact on survival. Methods: We identified MM patients from the Mayo Clinic Dysproteinemia Database who had at least one follow up FISH performed ≥6 months from diagnosis. The clinical characteristics, concomitant cytogenetic abnormalities, first line treatments administered, and OS were compared between patients with acquired 1q22 gain and patients who did not acquire this abnormality. The Mayo Clinic IRB approved this study. Results: A total of 1041 MM patients met the inclusion criteria. Of these, 63 patients (6.1%) had acquired 1q22 gain, defined as being negative for 1q22 gain on initial FISH at diagnosis and having this abnormality detected on subsequent FISH. Median age at diagnosis was 59 years and 56% were male. Median time to acquisition of 1q22 gain was 60 months (range 8-140 months). We identified one control patient for each case who was diagnosed within one year of the case and had a subsequent FISH performed at a similar duration from diagnosis. Patients with acquired 1q22 gain had similar baseline characteristics except for a higher proportion of high-risk (HR) FISH at diagnosis [t(4;14), t(14;16), t(14;20), and del(17p13)] when compared to controls (27% HR FISH versus 6% HR FISH; P<0.01). 1q22 gain was concomitantly present with trisomies in 33 patients (54%), monosomy 13 in 24 patients (39%), t(4;14) in 8 patients (13%), and del(17p13) in 7 patients (12%). All patients received treatment prior to acquisition of 1q22 gain. Of the 63 patients, first line induction therapy consisted of proteasome inhibitor (PI) with steroid in 43%, immunomodulatory drugs (IMiD) with steroid in 40%, and PI + IMiD with steroid in 17% of patients. 54 patients (85%) received upfront stem cell transplant (SCT) (median 5.9 months to SCT), compared to 50 patients (79%) in the control group who received SCT. The median follow up of all 126 patients was 6.8 years. There was a statistically significant reduction in median OS from diagnosis in patients with acquired 1q22 gain compared to the control group (10.8 years versus 13.0 years; P = 0.02; Figure 1). Predictors of acquisition of 1q22 gain were identified using a case-control method. Age ≥70 at diagnosis and presence of HR FISH at baseline appeared to increase the risk of acquiring 1q22 gain. Conclusion: Acquisition of 1q22 gain is a relatively uncommon occurrence, but notably reduced OS by 2.2 years compared to patients who did not acquire 1q22 during the course of their disease (P = 0.02). Older age and the presence of HR FISH at diagnosis increased the risk of acquisition of 1q22 gain. The presence of high-risk translocations at baseline suggests that acquisition of 1q22 gain occurs in the context of more aggressive disease biology. Disclosures Kapoor: Cellectar: Consultancy; Celgene: Honoraria; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Dispenzieri:Alnylam: Research Funding; Pfizer: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Intellia: Research Funding; Janssen: Research Funding. Gertz:Prothena: Consultancy; Celgene: Consultancy; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; NCI SPORE MM: Research Funding; Ionis/Akcea: Consultancy; Physicians Education Resource: Consultancy; Medscape: Consultancy, Speakers Bureau; Amgen: Consultancy; Appellis: Consultancy; Annexon: Consultancy; Spectrum: Consultancy, Research Funding; Janssen: Consultancy; Sanofi: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy. Dingli:Apellis: Consultancy; Rigel: Consultancy; Millenium: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Sanofi-Genzyme: Consultancy; Alexion: Consultancy; Janssen: Consultancy. Lin:Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy; Legend BioTech: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Kumar:Cellectar: Other; Genecentrix: Consultancy; Dr. Reddy's Laboratories: Honoraria; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Sanofi: Research Funding; Karyopharm: Consultancy; MedImmune: Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Adaptive Biotechnologies: Consultancy; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Carsgen: Other, Research Funding; Tenebio: Other, Research Funding.

Introduction: Since 2018, immunoenrichment-based matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX, has replaced immunofixation for the detection and isotyping of serum monoclonal proteins at Mayo Clinic. MASS-FIX has advantages including increased sensitivity, specificity, and the ability to distinguish therapeutic monoclonal antibodies. Herein, we report the laboratory characteristics and distribution of diagnoses of patients tested clinically at Mayo Clinic. Methods: MASS-FIX was performed on patient samples as previously described (Kohlhagen et. al. Clin Chem Lab 2020). Demographics and laboratory data, including quantitative M-spike, serum free light chains (FLC), and quantitative immunoglobulins at the time of MASS-FIX were recorded. For patients with multiple samples during the study period, only the initial MASS-FIX was evaluated. We identified 9195 unique patients with MASS-FIX performed between 7/24/2018 and 3/6/2020. Seven-thousand nine hundred and forty-six patients provided consent for study enrollment, and 7689 had data available on index diagnosis. Given considerable variability in the interpretation of diagnostic criteria for light chain (LC) MGUS, patients with this diagnosis (1360, 18%) were excluded. Patients were considered to have negative results (2211 in total) on MASS-FIX if: 1) no monoclonal protein was identified (1081, 49%); 2) the interpretation was "cannot rule out monoclonal protein" (945, 43%); 3) multiple, nonspecific spectral peaks were identified consistent with immune reconstitution (29, 1%); or 4) the only monoclonal protein identified was consistent with a therapeutic monoclonal antibody (156, 7%). Results: The final cohort consisted of 4118 patients with a positive MASS-FIX and 2211 patients with a negative MASS-FIX, all in the setting of underlying PCDs. Figure 1 illustrates the numbers and percentages of patients who are MASS-FIX positive versus MASS-FIX negative by diagnosis. MGUS and multiple myeloma (MM) were the most common diagnoses overall, and both were more common in the MASS-FIX positive cohort. More than 90% of patients with Waldenstrom's macroglobulinemia (WM), smoldering WM, smoldering MM, and cold agglutinin disease were positive by MASS-FIX. For MASS-FIX positive patients, IgG isotype was identified in 2575 patients (63%), IgA in 703 (17%) and IgM in 710 (17%). Bence Jones proteinemia was identified in 283 patients (7%) with lambda restriction being the most common (57%). 3625 patients (88%) had a monoclonal pattern, 228 patients (6%) had a bi-clonal pattern, and 7 (<1%) had a tri-clonal pattern. The majority of patients (58%) were kappa LC restricted by MASS-FIX, 222 (5%) had N-glycosylated LC, and 2 patients (<1%) had a heavy chain with no light chain. Conclusions: This single institution experience illustrates the practicality of MASS-FIX in detecting and following monoclonal proteins for a wide range of PCDs in a tertiary center. In this cohort, the percentage of patients who were MASS-FIX positive varied by diagnosis, reflecting cross sectional sampling of patients throughout their disease course. Disclosures Gertz: Research to Practice: Other; Springer Publishing: Patents & Royalties; Aurora Bio: Other; Johnson and Johnson: Speakers Bureau; Sanofi: Other; Amgen: Other: personal fee; Appellis: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Prothena: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Proclara: Other; DAVA oncology: Speakers Bureau; Celgene: Other; Teva: Speakers Bureau; Abbvie: Other; Physicians Education Resource: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau. Kumar:AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Carsgen: Other, Research Funding; Karyopharm: Consultancy; Merck: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Genecentrix: Consultancy; Adaptive Biotechnologies: Consultancy; Novartis: Research Funding; MedImmune: Research Funding; Sanofi: Research Funding; Tenebio: Other, Research Funding; Cellectar: Other; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments. Kapoor:Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Janssen: Research Funding; Celgene: Honoraria. Dingli:Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Alexion: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Apellis: Consultancy; Millenium: Consultancy. Lin:Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Gamida Cells: Consultancy; Takeda: Research Funding; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy. Murray:The Binding Site: Patents & Royalties: Patent Use of Mass Spec to identify monoclonal proteins licensed to The Binding Site. Dispenzieri:Alnylam, Intellia, Janssen, Takeda, Pfizer, Prothena, Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction Amyloidosis is a disease caused by aggregates of misfolded insoluble proteins that accumulate extracellularly and impair organ function. The most common type of systemic amyloidosis is immunoglobulin light chain (AL), which typically involves the heart, kidneys, nerves, liver, gastrointestinal tract and soft tissue. Retroperitoneal involvement in the setting of systemic AL amyloidosis is rare and only published as case reports. Aim To report characteristics and outcomes of AL amyloidosis patients that had retroperitoneal deposition of amyloid in the novel agent era. Methods Retrospective study of all consecutive systemic AL amyloidosis patients with retroperitoneal involvement at all three Mayo Clinic sites and at Davidoff cancer center, a tertiary hospital in Israel. All patients were diagnosed with retroperitoneal involvement based on computerized tomography (CT) scans. All patients had biopsy proof of amyloidosis with Congo red staining. Patients that were diagnosed with localized amyloidosis of the bladder or ureter and patients that did not receive systemic treatment were excluded. Results We identified 11 patients with systemic AL amyloidosis and retroperitoneal involvement between January 2001 and December 2018. Median age at diagnosis was 65 years (range 50-72). Ten were male (91%) and one was female. Five patients had amyloid secondary to B cell lymphoma (4 Waldenstrom macroglobulinemia and 1 had follicular lymphoma). The involved light chain was lambda in 7 patients and kappa in 4 patients. All patients were diagnosed with retroperitoneal involvement of amyloidosis at presentation (not at progression). In 10 out of the 11 patients, amyloidosis in the retroperitoneum was confirmed by a core biopsy of the retroperitoneal tissue. Significant unintentional weight loss (more than 5 kg) at presentation was documented in six patients (55%). Seven patients (64%) had enlarged lymph nodes on the CT scan. Three patients had CT finding of calcifications, and the distribution pattern was diffuse in 7 patients (64%), while 4 patients presented with a mesenteric mass. Six patients (55%) had evidence of amyloid deposits in the bone marrow and 3 patients (27%) had a positive fat pad. Periorbital purpura was observed in one patient and none had macroglossia. Therapy regimens used are described in table 1. Five patients underwent an autologous stem cell transplantation (ASCT). Eight patients (72%) presented with unilateral (N=2) or bilateral (N=6) hydronephrosis and 7 had nephrostomy tubes or stents inserted. The median follow-up from stent/nephrostomy tube insertion was 33 months (IQR 8-91). Regression of the deposition was documented in one patient and one patient was able to have his nephrostomy tube removed. One patient (9%) developed end stage renal disease requiring dialysis. Data regarding hematologic response rates were available for 9 patients and all responded and achieved hematologic PR or better. The median follow-up for all surviving patients was 91 months (IQR 27-179). Seven of the patients are currently alive. The median OS from diagnosis was 150 months. Figure 1 shows typical diffuse retroperitoneal involvement of AL amyloidosis on a CT scan. Review of the literature revealed 5 cases of retroperitoneal involvement of systemic AL amyloidosis. Most were reports published before routine typing of amyloid. Four of the five cases (80%) were male. The ages ranged from 46 to 80 years. Four of the five cases (80%) presented with weight loss. Two patients had calcifications on the CT scans, and one had a large pleural effusion. Conclusions We report a multicenter case series of 11 patients diagnosed with systemic AL amyloidosis with retroperitoneal involvement, all received systemic chemotherapy. We found male predominance in our cohort. Eight patients presented with hydronephrosis, and only one patient had the nephrostomy tube removed successfully after systemic therapy. ORR was 100% and median OS from diagnosis was 150 months, suggesting that retroperitoneal deposition might confer improved prognosis compared to the general amyloid population. Disclosures Kumar: Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Carsgen: Other, Research Funding; Genecentrix: Consultancy; Cellectar: Other; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Adaptive Biotechnologies: Consultancy; MedImmune: Research Funding; Novartis: Research Funding; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Tenebio: Other, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments. Dispenzieri:Intellia: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding. Dingli:Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Alexion: Consultancy; Apellis: Consultancy; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Karyopharm Therapeutics: Research Funding. Kapoor:Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Takeda: Honoraria, Research Funding. Gertz:DAVA oncology: Speakers Bureau; Appellis: Other: personal fee; Proclara: Other; Medscape: Other: personal fee, Speakers Bureau; Springer Publishing: Patents & Royalties; Annexon: Other: personal fee; Research to Practice: Other; Celgene: Other; Prothena: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Physicians Education Resource: Other: personal fee; Abbvie: Other; Johnson and Johnson: Speakers Bureau; Teva: Speakers Bureau; Janssen: Other: personal fee; Amgen: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Aurora Bio: Other; Sanofi: Other.

Background: Lytic bone lesions are one of the most common clinical characteristics of patients with multiple myeloma (MM) and identification of bone lesions help distinguish between patients with smoldering multiple MM and active MM. Given this, the most recent update of the diagnostic criteria for MM incorporates advanced imaging approaches for distinguishing between the two entities. Several small retrospective studies have compared conventional skeletal survey (SS) with whole-body low dose computed tomography (WBLDCT) scan or the CT portion of a positron emission tomography (PET) scan. Conducting prospective studies comparing these two modalities side by side is limited by the radiation exposure. We undertook this study to provide a comparison between these two imaging modalities in terms of their ability to recognize lytic bone lesions in patients with MM. Patients and methods: This was a retrospective study of consecutive patients with the diagnosis of MM treated at Mayo Cinic Hospital during 2004- 2018. Patients were included if they had a conventional skeletal survey no more than 3 months before MM diagnosis or any time after diagnosis and also had a WBLDCT or PET-CT within a 12-month period following the skeletal survey. We chose this approach since it is unlikely that a patient would have had both modalities done at the same time as part of standard of care (SOC). This approach was also facilitated by a gradual change in our SOC for skeletal imaging from conventional skeletal survey to WBLDCT. To measure the robustness of our findings, we performed a sensitivity analysis in patients who had the exam ≤6 months apart. Proportions were compared using a chi-square test and survival estimates were calculated using the Kaplan- Meier methodology and compared using log rank test. Results: The overall study cohort had 1040 patients, median age was 62 years at diagnosis (range, 24-94), 61% were male and 39% were female. The median time to the skeletal survey was 8 months from diagnosis (range, 0-160) and the median time to WBLDCT or PET-CT from SS was 2 months (0-12). A PET-CT was available in 789 (76%) of patients and WBLDCT in 251 (24%) of patients. Among the 300 patients with no lesions identified by SS, 188 (63%) had lytic lesions identified by CT, while in 60/740 (8%) patients with a positive SS did not have lytic lesions observed on the CT (p<0.0001). Overall, CT identified lytic lesions in 868 (84%) patients compared with 740 (71%) patients with lytic lesions seen on SS. Although the proportion of lytic lesions was slightly higher with PET compared to WBLDCT, the analysis did not reach statistical significance (65% vs. 56%; p = 0.17; Table 1a). After restricting the analysis to those with ≤6 months gap between low dose CT and SS (n=737), the result did not change (Table 1b). Further examination demonstrated that presence of lytic lesions by SS had no impact on OS from diagnosis, detection of lesions on the CT exam was associated with an inferior survival (112 vs. 81 months, p<0.0001). (Figure 1) Conclusion: Skeletal survey has been the screening technique of choice for evaluation of bone involvement in MM for decades. However, CT based approaches have higher sensitivity with lytic lesions identified in a higher proportion of patients. The prognostic value of lytic disease is evident with CT based detection, again suggesting that this provides a more accurate estimate of the skeletal disease burden. Low dose CT rather than conventional radiographs should be the modality of choice for monitoring disease-progression and diagnosing active multiple myeloma. Disclosures Kapoor: Cellectar: Consultancy; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria. Gertz:Abbvie: Other; Celgene: Other; Physicians Education Resource: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Janssen: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Johnson and Johnson: Speakers Bureau; Teva: Speakers Bureau; Annexon: Other: personal fee; Research to Practice: Other; Sanofi: Other; Proclara: Other; DAVA oncology: Speakers Bureau; Springer Publishing: Patents & Royalties; Appellis: Other: personal fee; Amgen: Other: personal fee; Prothena: Other: personal fee; Aurora Bio: Other; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee. Dispenzieri:Takeda: Research Funding; Pfizer: Research Funding; Janssen: Research Funding; Intellia: Research Funding; Alnylam: Research Funding; Celgene: Research Funding. Dingli:Alexion: Consultancy; Janssen: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Apellis: Consultancy; Karyopharm Therapeutics: Research Funding. Lin:Merck: Research Funding; Takeda: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Vineti: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gamida Cells: Consultancy. Kumar:Dr. Reddy's Laboratories: Honoraria; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Novartis: Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Carsgen: Other, Research Funding; Cellectar: Other; MedImmune: Research Funding; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding.

Background: Patients with newly diagnosed MM can be quite symptomatic as a result of end organ damage related to MM as well as presence of other comorbidities in this relatively older patient population. Prior studies have shown that the performance score as well as other quality of life (QOL), frailty and comorbidities scores can have prognostic value in these patients. However, many of these questionnaires are lengthy and complex, and not practical in a busy outpatient practice. We implemented a three question symptom assessment score in 2010 in our outpatient practice. Here we present the results of the analysis looking at the impact of this measurement in patients with newly diagnosed MM. Patients and Methods: Patients seen in the outpatient Hematology practice at Mayo Clinic, Rochester MN, were asked to grade the symptoms of fatigue, pain, and QOL on a 0 to 10 scale during the past 7 days, with 10 being the worst and the QOL on a similar scale but with 10 being the best. For the purpose of the current analysis the QOL score was reversed.These three scores were added for a total score. We looked at the impact of the baseline score as well as the score after four cycles of therapy, at the time of best response, and at the time of the first progression, wherever they were available. Survival curves were generated by the Kaplan-Meier method and compared using the log rank test. The Cox proportional hazards model was used for assessment of the impact of different prognostic variables. Results: Data from 735 patients with newly diagnosed MM seen at Mayo Clinic between 2011 and 2018 were available from baseline. The median total score was 10 (0-30), and for fatigue, pain and QOL were 4, 3 and 7 respectively, all with range of 0-10. Based on the baseline scores, patients were grouped into tertiles (Group 1 with score < 8, group 2 with score 8 to 14 and group 3 with a score ≥ 15). There were 256 (34%), 272 (37%) and 207 (28%) patients in groups 1, 2 and 3 respectively. The median overall survival (OS) (95% CI) from diagnosis was NR (7.9, NR), 7.7 (6.2, NR) and 5.4 (4.2, 6.9), respectively for groups 1, 2 and 3 (P < 0.0001) (Figure 1a). The prognostic value of the score was independent of age, FISH based risk status and the ISS stage. When evaluated after 4 cycles (n=325), the OS was significantly different for the 3 groups (P<0.01) (figure 1b). We then examined the impact of the score at best response to initial therapy (n=446) on OS from that timepoint and saw similar trend, but the results were not statistically significant (P=0.09) (Figure 1c). When evaluated at the time of first disease progression, the score again identified three groups with different OS from progression (P<0.001) (Figure 1d). Conclusions:Patient-reported outcomes are associated with survival in patients with MM. This simple, easy to complete patient-reported outcome 3-item scale can be easily completed in a busy practice and is a clinically useful tool to assess potential outcomes of patients at various disease stages, including at diagnosis and at relapse. Disclosures Kumar: Adaptive Biotechnologies: Consultancy; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Sanofi: Research Funding; MedImmune: Research Funding; Karyopharm: Consultancy; Tenebio: Other, Research Funding; BMS: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Carsgen: Other, Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Cellectar: Other; Genecentrix: Consultancy; Merck: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria. Kapoor:Janssen: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria. Gertz:Proclara: Other; Springer Publishing: Patents & Royalties; Abbvie: Other; Celgene: Other; Aurora Bio: Other; Medscape: Other: personal fee, Speakers Bureau; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Amgen: Other: personal fee; Appellis: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Prothena: Other: personal fee; Physicians Education Resource: Other: personal fee; Research to Practice: Other; Ionis/Akcea: Other: personal fee; Alnylam: Other: personal fee. Dispenzieri:Alnylam: Research Funding; Intellia: Research Funding; Janssen: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Pfizer: Research Funding. Dingli:Rigel: Consultancy; Millenium: Consultancy; Alexion: Consultancy; Janssen: Consultancy; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding. Lin:Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Legend BioTech: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding.

Proliferative glomerulonephritis with monoclonal immune deposits (PGNMID) and C3 glomerulopathy (C3G) with monoclonal gammopathy (MG) are kidney diseases related to monoclonal gammopathy of renal significance (MGRS). Rituximab or combination of cyclophosphamide, bortezomib and dexamethasone have been used with variable success but no clinical trial has been performed up to now. In this phase 2 trial, we evaluated the safety and efficacy of daratumumab (an anti-CD38 plasma therapy) in patients with PGNMID and C3G with MG. The primary objective was safety and tolerability of daratumumab. The secondary objective was the response rate to daratumumab. Response was defined by complete remission (CR) (proteinuria <500 mg/d and no more than 10% drop in eGFR) or partial remission (PR) (50% reduction in proteinuria with no more than 30% drop in eGFR) at 6 and 12 months. Daratumumab was administered intravenously at a dose of 16mg/kg once weekly for 8 weeks followed by once every other week for an additional 8 doses. Twelve patients were recruited. There was only one patient with C3G with MG recruited and one patient with PGNMID did not finish the first infusion of daratumumab. Both were excluded from evaluation of the secondary objective. The patient with C3G was excluded as later it was noted that the disease was not triggered by the MG but rather due to activation of her alternative complement pathway due to high-risk allele for complement Factor H (CFH) and C3. Mean age was 51.2 ± 22.6 (18-87) years. All patients were White and 5 were male. For the primary objective, there were five serious adverse events (SAE). Two were serious infections that occurred in the patient with C3G with MG. At the time of these infections, patient was receiving additional immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. One was a febrile episode attributed to a virus that resolved with stopping additional immunosuppression, and another was an episode of C. difficile colitis that resolved following treatment. There were 3 episodes of uncomplicated UTI that resolved following antibiotic therapy and one episode of URI that required no treatment. The other two SAE were eye chemosis and headache in the same patient that resolved. Last SAE was an episode of acute closed angle glaucoma that occurred 45 min into the 1st infusion. This patient was withdrawn from the study. The most common side effect was infusion related reaction (with first infusion) that included cough, congestion, and throat irritation that resolved by the end of the infusion. There were no grade 3 or 4 anemia, thrombocytopenia or leukopenia. At 6 months, 2 patients achieved CR, 6 achieved PR and 2 had no response (NR). At 12 months, the 2 patients who had NR had entered PR and 2 additional patients that had achieved PR entered CR, but 3 patients relapsed (1 from CR and 2 from PR group). Overall, at 12 months, 3 patients achieved CR, 5 achieved PR and 2 had NR (due to relapse). The median 24hr baseline urinary protein declined from 4346 mg (3245 - 7943) to 702 mg (435 - 3057), at 6 months (p=0.001) and 1264 mg (463 - 3645) at 12 months (p = 0.004). There was also significant improvement in serum albumin, hemoglobin, total and LDL cholesterol, and complement 3 levels from baseline to 12 months follow-up (Table 1). Estimated GFR remained unchanged from 61.1 ± 31.9 to 65.0 ± 31.7 at 12 months (p=0.4). In this trial, daratumumab has shown to be safe and well tolerated. Daratumumab was also shown to be effective in reducing the proteinuria dramatically in patients with PGNMID secondary to MGRS along with stabilization of renal function. In conclusion, this is the first clinical trial of daratumumab in patients with MGRS and the promising results deserves further study. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Daratumumab - off label use for treatment of PGNMID

Introduction: Since 2018, immunoenrichment-based matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX, has replaced standard gel-based immunofixation for the detection and isotyping of serum monoclonal proteins at Mayo Clinic. MASS-FIX can readily identify N-glycosylation of involved light chains (LC N-glycosylation) by its unique, polytypic spectral pattern. LC N-glycosylation is identified more commonly in light chain amyloidosis (AL) than other plasma cell disorders (PCDs), and is associated with an increased risk of progression from MGUS to both AL and other PCDs (Dispenzieri et. al. Leukemia 2020). Herein, we report the mass spectral characteristics and distribution of diagnoses among 222 patients with LC N-glycosylation detected during a 20 month period in our clinical lab. Methods: MASS-FIX was performed on patient samples as previously described (Kohlhagen et. al. Clin Chem Lab 2020). Demographics and laboratory data, including quantitative M-spike, serum free light chains (FLC), and quantitative immunoglobulins at the time of MASS-FIX were recorded. For patients with multiple samples during the study period, only the initial MASS-FIX was evaluated. 9195 unique patients had MASS-FIX performed from 7/24/2018 to 03/06/2020. Inclusion criteria for this retrospective study included: 1) consent for record review; 2) a monoclonal protein identified on MASS-FIX; 3) an underlying PCD. Patients were considered to have negative results (2211 in total) on MASS-FIX if: 1) no monoclonal protein was identified (1081, 49%); 2) the interpretation was "cannot rule out monoclonal protein" (945, 43%); 3) multiple, nonspecific spectral peaks were identified consistent with immune reconstitution (29, 1%); or 4) the only monoclonal protein identified was consistent with a therapeutic monoclonal antibody (156, 7%). The final positive cohort consisted of 4118 patients with definitive monoclonal proteins on MASS-FIX. Results: Two-hundred and twenty-two (5%) of the 4118 patients with a positive MASS-FIX had LC N-glycosylation. 202 patients (91%) had FLC assays performed. Of these, 110 (54%) were kappa LC restricted, 22 (11%) were lambda restricted, and 70 (35%) were normal. A quantifiable M-spike was identified in 110 patients (85%) of 129 patients who had serum protein electrophoresis performed. By MASS-FIX, 139 patients (63%) had an IgG isotype, 18 (8%) an IgA, and 55 (25%) an IgM. Two of these patients had a bi-clonal pattern in which both IgG kappa and IgM kappa LCs were N-glycosylated. 12 patients (5%) had monoclonal light chains with no corresponding heavy chain. Overall, 173 (78%) of 222 patients were kappa LC restricted and 44 (22%) were lambda. 189 patients (85%) had a monoclonal pattern, 18 (8%) had a bi-clonal pattern, and 3 (1%) had a tri-clonal pattern. The most common PCD diagnoses for the 222 patients with LC N-glycosylation were MGUS (45%), multiple myeloma (MM) (31%), and immunoglobulin light chain amyloidosis (AL) (8%). The percentage of MASS-FIX positive patients with LC N-glycosylation by diagnosis, stratified by kappa and lambda LC restriction, is illustrated in Figure 1. Cold agglutinin disease (CAD) had the highest relative percentage of patients with LC N-glycosylation, regardless of LC restriction. Eighteen AL patients (5%) had LC N-glycosylation; the percentage was higher in kappa restricted (13%) than lambda restricted AL patients (2%). Of note, LC N-glycosylation was not detected in patients with plasma cell leukemia, non-AL amyloidosis with associated MGUS, POEMS Syndrome or Castleman's Disease in this cross sectional sampling of patients. Conclusions: This retrospective study demonstrates that 5% of patients in a routine clinical setting with positive MASS-FIX have glycosylated LCs. Consistent with prior observations, CAD had the highest relative percentage of LC N-glycosylated patients. The percentage of AL patients with LC N-glycosylation in this cohort is lower than previously reported for newly diagnosed AL patients (Kumar et. al. Leukemia 2019), which is not surprising given that the current cohort study is a cross sectional evaluation of patients at various stages of diagnosis and treatment rather than a prevalence study. Further study will be done to exclude the presence of latent AL in patients with N-glycosylated LC and diagnoses of MGUS, SMM, MM, and Waldenstrom's macroglobulinemia. Disclosures Gertz: Springer Publishing: Patents & Royalties; Proclara: Other; DAVA oncology: Speakers Bureau; Johnson and Johnson: Speakers Bureau; Teva: Speakers Bureau; Sanofi: Other; Research to Practice: Other; Celgene: Other; Abbvie: Other; Physicians Education Resource: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Amgen: Other: personal fee; Appellis: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Prothena: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Aurora Bio: Other. Kumar:Adaptive Biotechnologies: Consultancy; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Carsgen: Other, Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Merck: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; MedImmune: Research Funding; Genecentrix: Consultancy; Tenebio: Other, Research Funding; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Novartis: Research Funding; Kite Pharma: Consultancy, Research Funding; Cellectar: Other. Kapoor:Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria; Cellectar: Consultancy. Dingli:Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; Sanofi-Genzyme: Consultancy; Apellis: Consultancy; Rigel: Consultancy; Millenium: Consultancy. Lin:Janssen: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Legend BioTech: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Murray:The Binding Site: Patents & Royalties: Patent Use of Mass Spec to identify monoclonal proteins licensed to The Binding Site. Dispenzieri:Intellia: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Alnylam: Research Funding.

Introduction: The utility of amyloidosis staging systems has been validated for newly diagnosed patients, but their role in restaging after starting treatment has not been explored. Given the high early mortality in this disease, restaging remote from the diagnosis may have clinical value. We designed this study to evaluate whether the currently used staging systems are prognostic when applied at 3 and 6 months from starting first-line treatment, and whether stage migration impacts survival. Methods: This is a retrospective study including patients with systemic light chain amyloidosis diagnosed between January, 1st 2006 and June, 30th 2019 and were seen in Mayo Clinic, Rochester, MN within 90 days of diagnosis; the analysis included 535 and 301 patients who had restaging data available for at least one of the staging systems at 3 and 6 months, respectively. Patients were grouped into 4 stages using the 2015 European modification of the Mayo 2004 staging system based on values of cardiac biomarkers (cardiac troponin T and NTproBNP), and using the Mayo 2012 staging system based on cardiac biomarkers and the difference in serum free light chain concentration (dFLC). Overall survival (OS) was calculated from the time of re-staging until death or last follow up. Results: Using the modified Mayo 2004 staging system at 3 months from starting first-line treatment, median OS was 11.8 [95%CI: 11.4-not reached (NR)], 10.8 (95%CI: 9.4-NR), 4.6 (95%CI: 2.8-6.7), and 1.1 (95%CI: 0.7-2.6) years in patients with stage I, II, IIIa, and IIIb, respectively. Using Mayo 2012 staging at 3 months, OS was 11.8 (95%CI: 10.9-NR), 9.0 (95%CI: 6.2-NR), 5.2 (95%CI: 3.3-6.1), and 0.8 (95%CI: 0.7-1.1) years in patients with stage I, II, III, and IV, respectively (Figure 1a &b). Using the modified Mayo 2004 staging system at 6 months from starting first-line treatment, median OS was NR (95%CI: NR-NR), 9.8 (95%CI: 6.2-NR), 5.4 (95%CI: 3.2-9.0) and 0.9 (95%CI: 0.6-3.7) years in patients with stage I, II, IIIa, and IIIb, respectively. Using Mayo 2012 staging at 6 months, OS was NR (95%CI: 8.4-NR), NR (95%CI: 7.9-NR), 4.6 (95%CI: 3.0-6.5), and 0.9 (95%CI: 0.2-1.8) years in patients with stage I, II, III, and IV, respectively (Figure 1c &d). On multivariate analysis, advanced (stage > 2) modified Mayo 2004 stage (HR: 1.6, P=0.004) and advanced (stage > 2) Mayo 2012 stage (HR: 2.4, P<0.001) at 3 months were associated with decreased survival independent of cardiac response, hematologic response, and transplantation status. Although advanced Mayo 2004 stage at 6 months was associated with decreased survival, it was not statistically significant (HR: 1.5, P=0.09). In contrast, advanced Mayo 2012 stage at 6 months was independently associated with decreased survival (HR: 2.1, P=0.02). For both systems, worsening stage at 3 months or at 6 months was associated with a worse survival than retaining the original stage. In contrast, improving stage as compared to remaining in same stage was not associated with better survival at 3 or 6 months (Table 1). When the analysis was restricted to patients who had an advanced stage at diagnosis, improving stage at 3 months was associated with longer survival compared to retaining the original stage, with both modified Mayo 2004 (10.8 vs. 3.3 years, P<0.001) and Mayo 2012 (8.1 vs. 2.6 years, P<0.001) staging systems. At 6 months, stage improvement was associated with longer survival than retaining the original stage when the modified Mayo 2004 staging system was used (NR vs. 5.0 years, P=0.02), but it was not statistically significant when the Mayo 2012 staging system was used (5.9 vs. 3.7 years, P=0.12). Conclusion: The modified Mayo 2004 and the Mayo 2012 staging systems have independent prognostic value when used for restaging after 3 and 6 months from initiation of first-line treatment. Migration to a higher stage from diagnosis predicts decreased survival, compared to retaining the same stage. Stage improvement is associated with a better OS in patients with advanced stage at diagnosis. Disclosures Dispenzieri: Alnylam, Intellia, Janssen, Takeda, Pfizer, Prothena, Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kapoor:GlaxoSmithKline: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Cellectar: Consultancy. Dingli:Rigel: Consultancy; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Lin:Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gamida Cells: Consultancy; Takeda: Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Janssen: Consultancy, Research Funding; Vineti: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Gertz:Alnylam: Consultancy; NCI SPORE MM: Research Funding; Ionis/Akcea: Consultancy; Amyloidosis Foundation: Research Funding; Celgene: Consultancy; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Consultancy; Springer Publishing: Patents & Royalties; Prothena: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; International Waldenstrom Foundation: Research Funding. Kumar:Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Genecentrix: Consultancy; Cellectar: Other; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Kite Pharma: Consultancy, Research Funding; MedImmune: Research Funding; Carsgen: Other, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Novartis: Research Funding; Adaptive Biotechnologies: Consultancy; Tenebio: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Sanofi: Research Funding.

Recent advances in the fields of hematology and oncology over the past decades are truly astounding. Higher response rates have increased the overall and progression free survival, and for certain cancers, have brought the possibility of a cure within reach. While this represents great news for many cancer patients, their longer survival is creating new challenges. Cancer patients can now live long enough to develop chronic kidney disease (CKD), receive long term dialysis, and even a kidney transplantation. There are important and significant knowledge gaps in the care of the cancer patient with CKD or end stage renal disease (ESRD). The subspecialty of Onco-Nephrology was created with the goal of optimizing the care of cancer patients with CKD or ESRD by (1) identifying crucial knowledge gaps in the proper care of these patients by (2) engaging in basic science and clinical research independently and in partnership with cancer specialists to attenuate these gaps, and (3) by educating future onco-nephrologists.