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AbstractThe diagnosis of primary plasma cell leukemia (pPCL) has been made by quantifying circulating plasma cells (cPCs) morphologically on a peripheral blood (PB) smear. However, this technique is not sufficiently sensitive. Multiparametric flow cytometry (MFC) provides a readily available and highly sensitive method to identify and quantify cPCs that could complement PB smear assessment. However, an optimal quantitative cutoff for cPCs by MFC to identify pPCL has not been established. Thus, a total of 591 patients newly diagnosed multiple myeloma (NDMM) patients who had their PB samples evaluated morphologically by PB smear, and immunophenotypically by MFC prior to beginning therapy were evaluated. The presence of ≥200 cPCs/μL by MFC (N = 25 or 5% of the total population) was chosen to identify patients with ≥5% cPCs by PB smear with a specificity of 99% and a sensitivity of 77%. For patients with ≥200 cPCs/μL by MFC compared to the remainder of the cohort, the median Time to next therapy (TTNT) was 18 vs 30 months and the median OS was 38 vs 70 months respectively. Thus, MFC assessment of PB can be utilized in conjunction with the morphological assessment of a PB smear to aid in improving the identification of pPCL among NDMM patients.

Background: The current commonly used regimens in newly diagnosed multiple myeloma (NDMM) utilize steroids (dexamethasone or prednisone) in various combinations: bortezomib, lenalidomide and dexamethasone (VRd), bortezomib, thalidomide and dexamethasone (VTd), daratumumab, lenalidomide and dexamethasone (DRd) and daratumumab, bortezomib, melphalan and prednisone (DVMP). However, steroid therapy may be associated with various adverse effects, including, but not limited to mood changes, insomnia, hypertension, hyperglycemia, osteoporosis, adrenal suppression, muscle weakness, and increased risk of opportunistic infections. A recent trial demonstrated improved tolerability of a regimen (Rd-R) involving an abbreviated course of dexamethasone, without compromising the efficacy in patients with intermediate-fit NDMM (Lorocca A., et al., ASH 2018). We designed a phase 2 clinical trial to examine the safety and efficacy of daratumumab, an anti-CD38 monoclonal antibody in combination with an all-oral regimen of ixazomib, a proteasome inhibitor, lenalidomide, an immunomodulatory drug, and modified dose dexamethasone (IRd). Patients and Methods: NDMM patients with measurable disease and adequate organ function were enrolled, irrespective of their transplant eligibility. The primary objective was to determine the rate of complete response (CR) to daratumumab-IRd. Treatment consisted of daratumumab, 16 mg/kg, weekly for two cycles, every other week during cycles 3-6 and then every 4 weeks, ixazomib, 4 mg days 1, 8, 15, lenalidomide, 25 mg days 1-21, and dexamethasone upto 40 mg intravenously weekly for no more than two cycles, followed by use only as a prophylactic premedication for daratumumab-associated infusion reactions. Myeloma risk stratification was assessed by cytoplasmic immunoglobulin fluorescence in-situ hybridization (cIg FISH) analysis. Results: Overall, 40 patients were accrued, with data available on all patients for analysis at the cutoff date of July 19, 2019. The median age at enrollment was 64.5 (33-81) years; 37.5% were female. Eight (20%) patients were high risk by FISH. The median number of cycles was 6 (2-11) and the median follow up was 6.1 (2-11.7) months. Among 40 patients who had received at least 2 cycles of therapy, responses were attained rapidly; at the end of cycle 2, 88% patients achieved at least a partial response and 33% at least a very good partial response (VGPR) that improved to 52% at the end of 4 cycles among 29 patients who had completed at least 4 cycles. The overall best confirmed response rate among all 40 patients (Figure 1) was 95%, including 10% stringent CR, 5% CR and 23% near CR (13% VGPR excluding nCR). Stem cell collection was completed in 17 patients so far, all of whom required filgrastim and plerixafor. The median CD34+ cell count was 7.7 (range 2.9-11.6) million/kg . All patients were alive and 39 (97.5%) patients were progression-free at last follow up. Four (10%) patients proceeded to autologous stem cell transplantation off study, per patient and/or investigator discretion (1 in CR, 2 in PR, 1 with progressive disease). Overall, 224 cycles have been administered across the study, with dose reduction/ hold required in a subset of patients; ixazomib (10%), lenalidomide (20%), daratumumab (0%) and dexamethasone (13%); the most frequent reasons for dose adjustment were skin rash and hematologic toxicities. A grade 3 or higher adverse event, at least possibly attributed to the study drugs, was observed in 40% of patients; hematologic in 30% (lymphopenia 25%, neutropenia 15%, thrombocytopenia 5% and anemia 2.5%) and non-hematologic in 18% of patients (hyperglycemia 8%, diarrhea 5%, infections 5%, ileus 2.5%, maculopapular rash 2.5%, and fatigue 2.5%). Updated results with additional 6 months of follow up and minimal residual disease assessment related data will be presented at the meeting. Conclusion: Our early results suggest that the combination of daratumumab, ixazomib, lenalidomide and modified dose dexamethasone is well-tolerated, with excellent activity, and does not adversely impact stem-cell mobilization in patients with NDMM. Disclosures Kapoor: Takeda: Honoraria, Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Janssen: Research Funding; Glaxo Smith Kline: Research Funding; Cellectar: Consultancy. Gertz:Spectrum: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Prothena: Honoraria; Alnylam: Honoraria; Ionis: Honoraria. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Dispenzieri:Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. OffLabel Disclosure: Daratumumab in combination with Ixazomib, lenalidomide and dexamethasone for the management of newly diagnosed multiple myeloma

Introduction: Advances in the understanding of disease biology, the introduction of new drugs, and better supportive care have improved outcomes in multiple myeloma (MM). Most improvements have been observed in clinical trial and tertiary referral center populations but questions remain about the generalizability of these findings to patients treated in the community. Methods: We studied all patients diagnosed with MM between 01/01/2001 and 12/31/2015 who had complete demographic and overall survival (OS) data available and were seen at Mayo Clinic (MAYO) or followed in the Surveillance, Epidemiology, and End Results Program (SEER, 18 registry data 2000 - 2016, 11/2018 submission). We retrieved age at diagnosis, sex, date of diagnosis, date of last follow-up, and OS for all patients. OS was defined as the time from diagnosis to death from any cause. Patients who were alive at the end of follow-up (12/31/ 2016) were censored. OS estimates were calculated using the Kaplan-Meier method. Age- and sex-adjusted Cox models were used to assess the association between the 5-year interval of diagnosis and OS. Expected OS estimates were calculated based on United States general population rate tables (Human Mortality Database) using a conditional approach. Standardized mortality ratios (SMR) were calculated by dividing the number of observed deaths by the number of expected deaths in age- and sex-matched general United States population controls. Linear regression models were fit to test for linear trends in early mortality and SMR over time (per 5-year interval). P-values below 0.05 were considered statistically significant. Results: The median age at diagnosis was 3 years lower in patients at MAYO (64 years, 15% ≥ 75 years, 60% male, n = 3293) compared to SEER (67 years, 29% ≥ 75 years, 55% male, n = 61779). After a median follow-up of 2.8 years the median OS was longer in MAYO compared to SEER (5.4 versus 4.0 years, HR 0.82, 95% CI 0.78 - 0.86, p < 0.001) and remained statistically significant after adjusting for age and sex (HR 0.91, 95% CI 0.86 - 0.95, p < 0.001). Early mortality (1-year mortality) decreased between 2001-2005 and 2011-2015: From 20% to 11% at MAYO and from 26% to 19% in SEER. When grouping OS by year of diagnosis (in 5-year-intervals) improvements were seen in both populations (A) and remained statistically significant after adjusting for age and sex. The relative improvements were similar comparing the 5-year period after the introduction of the novel therapies (2006 - 2010) to 2001 - 2005 and more pronounced in MAYO for the most recent 5-year interval (2011 - 2015, A). This trend was reflected in a steady temporal improvement in 5-year OS estimates in MAYO including the most recent 5-year interval (2011 - 2015, B bottom left). In SEER there was a comparable increase between the first two 5-year intervals but a lesser improvement in more recently (2011 - 2015, B bottom left). A diagnosis of MM remained associated with significant excess mortality in all age groups over time in both populations (B top). There was a decrease in excess mortality over time at MAYO (SMR decline per 5-year interval 1.3, 95% CI 0.9 - 1.8, p < 0.001) while there was little change in SEER (SMR decline 0.0, 95% CI -0.3 - 0.3, p = 0.917, B bottom right). Further stratifying by age at diagnosis, the decrease in excess mortality was observed mostly in patients < 75 years at MAYO (SMR decline per 5-year interval 1.7, 95% CI 1.5 - 2.0, p < 0.001, C bottom left) and to a lesser extent in older patients (SMR decline 0.4, 95% CI 0.2 - 0.6, p < 0.001, C bottom right). No such trends towards improvement were observed in either age group in SEER (C bottom). In older patients, early mortality remained approximately 30% in both populations despite continued improvements, while the 5-year OS estimates for the most recent 5-year interval (2011 - 2015) were 37% at MAYO and 26% in SEER (C top). Conclusions: Both early mortality and long-term survival have improved over time. Reductions in excess mortality were largely confined to younger patients with access to specialized care. Patients ≥ 75 years represent more than a quarter of all patients in the community, a third of them died within one year of the diagnosis, and only one in four was alive five years later. Older patients with MM remain a vulnerable population and have derived only limited benefit from recent advances in the field. Safe and effective therapies for older patients with MM remain an unmet need. Figure Disclosures Gertz: Ionis/Akcea: Consultancy; International Waldenstrom Foundation: Research Funding; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding. Dispenzieri:Alnylam: Research Funding; Akcea: Consultancy; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Celgene: Research Funding. Lacy:Celgene: Research Funding. Maurer:Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kapoor:Takeda: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Smith Kline: Research Funding; Cellectar: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Key PointsPatients with an abnormal sFLC ratio because of LC suppression have outcomes similar to those with a normal ratio. sFLC ratio has prognostic value in patients achieving CR who have an absence of clonal BMPCs assessed by MFC.

AbstractOur prior studies identified the prognostic significance of quantifying cPCs by multiparametric flow cytometry (MFC) in newly diagnosed multiple myeloma (NDMM) patients. We evaluated if a similar quantification of cPCs could add prognostic value to the current R‐ISS classification of 556 consecutive NDMM patients seen at the Mayo Clinic, Rochester from 2009 to 2017. Those patients that had ≥5 cPCs/μL and either R‐ISS stage I or stage II disease were re‐classified as R‐ISS IIB stage for the purposes of this study. The median time to next therapy (TTNT) and overall survival (OS) for patients with ≥5 cPCs/μL at diagnosis was as follows: R‐ISS I (N = 110) ‐ 40 months and not reached; R‐ISS II (N = 69) ‐ 30 and 72 months; R‐ISS IIB (N = 96) ‐ 21 and 45 months and R‐ISS III (N = 281) ‐ 20 and 47 months respectively. Finally, ≥ 5 cPCs/μL retained its adverse prognostic significance in a multivariable model for TTNT and OS. Hence, quantifying cPCs by MFC can potentially enhance the R‐ISS classification of a subset of NDMM patients with stage I and II disease by identifying those patients with a worse than expected survival outcome.

AbstractHistological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88 L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88 L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high‐grade lymphoma, with median time‐to‐transformation of 4.5 (range 0‐21) years in the transformed cohort. The MYD88 L265P mutation status was known in 435/1147 (38%) patients (406 with non‐transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88 WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1‐23]; P = .003). Additionally, the MYD88 WT status was independently associated with shorter time‐to‐transformation (HR 7.9 [95%CI: 2.3‐27; P = .001]), with a 5‐year transformation rate of 16% for MYD88 WT vs 2.8% with MYD88 L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8‐6.8; P < .001). In conclusion, the MYD88 WT status is an independent predictor of transformation and associated with a shorter time‐to‐transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.

Abstract Background: Normalization of serum free light chain ratio (FLCr) following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma, and is associated with improved overall survival (OS). However, its value in patients achieving less than a CR is not clear. We hypothesized that patients in whom FLCr normalizes with the initial anti-myeloma therapy will have an improved outcome, even in the absence of a CR. Methods: We analyzed the medical records of patients with MM who were evaluated at Mayo Clinic, Rochester, MN between January 2004 and December 2011, seen within 90 days of diagnosis. We selected patients with measurable disease on serum protein electrophoresis, defined as a serum M-spike ≥1 g/dl at the time of diagnosis. Then, we excluded all patients with negative immunofixation for monoclonal M-protein in serum and urine at their first response as well as those who did not have serum FLC results available from the time of their first best response. M protein measurements were collected serially from the time of diagnosis until the time of the first relapse or last follow up date if no relapse was recorded. Progression-free survival (PFS) and OS were analyzed using the Kaplan-Meier method. Results: Out of the 1354 MM patients seen at our institution during this period, a total of 453 patients were included in our study. The median age of the cohort at the time of diagnosis was 65 (range, 29-91); 49% were older than 65 years and 284 (63%) were male. The estimated median follow up for the whole cohort was 66 months (95% CI; 61, 71); 241 patients were alive with a median follow up of 4.7 years (range, 0.4 to 10). Three hundred and seventy three (82%) patients had relapsed following the initial therapy with a median time to progression (TTP) of 19.5 months (95% CI; 18, 22) and PFS of 19 months (95% CI; 17, 20). The median OS for the entire cohort is 67 months (95% CI; 59, 73). The median time to the best first response was 6.9 months (range: 0.3-83 months). At the time of the best first response 154 patients (34%) had normal FLCr. Patients with normal FLCr had a longer PFS (29 vs. 16 months, P< .0001) and OS (91 vs. 58 months, P= .0002). We then examined the impact of FLCr normalization on survival outcomes according to their IMWG response categories. We found that FLCr normalization had a favorable impact on PFS in each of the three groups [very good partial response (VGPR), Partial response (PR), and Stable disease (SD)], However, when looking at the OS, only patients with PR had a better OS associated with a normal sFLC κ/λ ratio (Table 1). Conclusions: Obtaining a normal sFLC ratio appears to confer a more favorable prognosis irrespective of the depth of the response, suggesting an important role for serial-sFLC measurements in disease monitoring even in patients who achieve only a PR to therapy as their best response. This supports the inclusion of sFLC at all levels of response included in the current International Myeloma Working Group (IMWG) criteria. Abstract 3427. Table 1 Effect of FLCr normalization according to IMWG response categories SD PR VGPR Normal FLCr Abnormal FLCr p-value Normal FLCr Abnormal FLCr p-value Normal FLCr Abnormal FLCr p-value Number of patients 7 70 62 157 85 60 PFS, month, median (95% CI) 27 (14, 36) 7 (5, 12) < .02 26 (20, 36) 17 (13, 20) .0005 29 (23, 32) 21 (18, 26) .03 OS, months, median (95% CI) 68 (49, 68) 41 (31, 61) > .1 NR (65, NR) 61 (50, NR) .004 74 (67, 107) 73 (59, NR) > .9 • Abbreviations: NR; statistically not reached •• Progressive disease (PD) was not included because none of the 12 patients achieved a normal FLCr. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Multiple Myeloma (MM) patients have a substantially reduced Health related Quality of Life (HQOL) at diagnosis (dx) due to disease related symptoms like bone pain (58%) and fatigue (32%). HQOL monitoring is becoming increasingly important, owing to improved survival and the impact of treatment-related toxicity. As a result HQOL assessments are increasingly being used in clinical trials, but the literature regarding the relationship between HQOL and outcomes in MM is sparse. We used the Mayo Clinic “Hematology Patient Reported Symptom Screen” (HPRSS) to assess the impact of HQOL on outcomes in newly dx patients with MM. Methods:We retrospectively reviewed charts of 453 patients with newly dx MM seen at Mayo Clinic, Rochester from 2009 to 2014. All patients who visit Mayo clinic hematology clinic complete a 3-point questionnaire (HPRSS) on pain, fatigue and quality of life (QOL) (scored on a scale of 0-10; with 0 being the least fatigue or pain and 10 being the best QOL). Pain, fatigue and QOL scores documented at the time of dx and at 6 months were collected. JMP version 10 was used for the data analysis. Results: The median age at diagnosis was 67 years (range, 33-95); 60% were male. The estimated median OS for the cohort was 21 m (95% CI19, 23); 387 (85%) of the patients were alive at last follow up and the median OS for the population was not reached. The median (IQR) scores for pain, fatigue and QOL were 4 (2, 6), 3 (1, 5), and 7 (5, 9), respectively. First, we examined the relationship between each of the scores (dichotomized at the median) and the baseline characteristics. Higher fatigue scores were associated with lower Hb and serum albumin and higher beta 2 microglobulin, LDH and marrow plasmacytosis. Higher pain scores were seen in female patients, and associated with higher B2M, serum calcium and lytic bone lesions. Lower QOL scores were associated with lower absolute lymphocyte count and serum albumin levels. Next, we examined the relationship between the scores and the OS from diagnosis. The overall survival was inferior for patients with higher pain scores, fatigue scores and lower QOL scores (Figure). In a multivariable analysis, fatigue scores were most strongly associated with survival outcome. Patients with adverse scores in two or more of pain, fatigue and QOL had significantly inferior outcomes (Figure). In univariate analysis, age, B2M, LDH, FISH high risk and the presence of two or more adverse scores were all significantly associated with poorer OS. In a multivariable analysis, age, LDH and the presence >=2 adverse scores were all associated with shorter OS. Of the 453 patients included in the study, 222 patients had pain, fatigue and QOL scores at 6 month from diagnosis. At 6 months, the median (IQR) scores for pain, fatigue and QOL were 2 (1, 5), 4 (2, 5), and 7 (5, 9), respectively; suggesting improved pain, worsened fatigue and static QOL scores. Improvement in the scores by at least one point was seen in 50%, 49% and 38% for the fatigue, pain and QOL scores. While the pain and fatigue scores at 6 months correlated inversely with OS, improvements in the scores in any of the three were not associated with any improved outcomes. Conclusion: A simple, patient reported scoring system for pain, fatigue, and overall perceived QOL at the time of diagnosis is a powerful predictor of survival outcomes in patients with newly diagnosed MM and should be considered routinely in clinical practice. The results of these patient reported measures can be utilized to develop risk-adapted trials in patients with MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: pPCL is a rare and aggressive form of multiple myeloma (MM) with poor survival outcomes compared to that experienced by MM patients. It has been traditionally defined by the presence of an absolute plasma cell count of > 2000/microL or >20% circulating plasma cells (cPCs) in the peripheral blood. However, several recent studies have validated the optimal cutoff for defining pPCL to be >5% cPCs on a peripheral blood smear due to equally poor outcomes in this less restrictive cohort. Hence, given the rarity of this disease entity, we evaluated the clinical outcomes and cytogenetic features of patients diagnosed with pPCL at our institution with the new proposed definition of pPCL by >5% cPCs on peripheral blood smear that were treated with novel agent induction therapies. METHODS: We evaluated all patients with pPCL diagnosed between 2000 - 2018 evaluated at Mayo Clinic in Rochester, Minnesota. Data regarding these patients were extracted from a prospectively maintained database and from the review of the electronic medical records. Patients were categorized as having high risk cytogenetics if any of the following abnormalities were present: del 17p, t(4;14), t(14;16) or t(14;20). Chi-square tests and Fisher exact tests were used to compare differences between the sub-groups of interest. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. RESULTS: This cohort consisted of 71 patients with pPCL with a median age of 62 years (range: 34-91) of which 33 (46%) were male. The median follow up was 46 months (95% CI: 41 - 90). The median bone marrow plasma cell content was 84% (Range: 10 - 100) and the median plasma cell percentage on the peripheral smear was 23% (range: 5 - 93). There were 48 (68%) patients with >20% cPCs in their peripheral blood smear. Only 23 (32%) patients had concurrent information on the number of cPCs by multiparametric flow cytometry at diagnosis and the median number of cPCs detected was 32,807 per 150,000 events analyzed (Range: 354 - 132,256). There were 15/54 (28%) patients who presented with a creatinine of 2 mg/dL or greater and 17/55 (31%) pts who presented with hypercalcemia (11 mg/dL or greater). Data for ISS classification was available in 45 patients and is as follows: Stage 1- 3 (7%) patients, Stage 2- 10 (22%) patients and Stage 3- 32 (71%) patients. Data on the presence of primary cytogenetic abnormalities were available in 60 (85%) patients of which 29 (49%) had high risk cytogenetics. The distribution of primary cytogenetic abnormalities among this cohort was as follows: t(11;14) - 27 (45%), t(4;14) - 5 (8%), t(14;16) - 8 (13%), t(14;20)- 3(5%) and del 17p- 15(25%). All patients received novel agent induction therapy with 40 (57%) of them having received at least one autologous stem cell transplant and 1 patient undergoing an allogeneic stem cell transplant. The median overall survival (OS) for all pPCL patients in this cohort was 23 months (95% CI: 19 - 38). The OS was similar in patient with 5-19% cPCs vs. >20% cPCs (24 vs. 23 months, P = 0.999). However, when the entire cohort was stratified by cytogenetic risk, the median OS was 51 months for standard risk vs. 19 months for high risk (P = 0.005) (FIGURE). There were only 17 (30%) patients in this cohort who were alive for 48 months or longer since diagnosis (i.e. twice the median OS of this cohort) and they were more likely to not have high risk cytogenetics at diagnosis (P = 0.05). CONCLUSION: In this analysis of one of the largest contemporary cohorts of pPCL patients, the outcomes of patients diagnosed with pPCL remain poor despite the use of novel agent induction therapy. However, some patients appear to do better than expected and this phenomenon may be influenced by the absence of high risk cytogenetics. Disclosures Kumar: Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Lacy:Celgene: Research Funding. Kapoor:Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Janssen: Research Funding. Russell:Imanis: Equity Ownership. Leung:Omeros: Research Funding; Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees. Gertz:Celgene: Consultancy; Prothena Biosciences Inc: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Janssen: Consultancy; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Annexon: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Spectrum: Consultancy, Research Funding; i3Health: Other: Development of educational programs and materials; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau.