Sidana, Surbhi

8023 Background: MGTA-145 (GroβT), a CXCR2 agonist, has shown promising activity for HSC mobilization with plerixafor in pre-clinical models and healthy volunteers. Methods: This phase 2 single center study evaluates HSC mobilization with MGTA-145 + plerixafor and same day apheresis in patients with multiple myeloma. Patients received plerixafor 0.24 mg/kg (0.16 mg/kg if renal dysfunction) SQ, followed 2 hours later by MGTA-145 (0.03 mg/kg) IV over 3-10 minutes and apheresis within 30 minutes. Mobilization was repeated for a second day if day 1 yield was < 6 x 106 CD34+ cells/kg. This interim analysis reports on mobilization in 10 patients (of 25 planned), including safety cohort of first 6 patients completing transplant. Primary endpoint is collection of 2 x 106 CD34+ cells/kg. Results: Median age was 63 years (range: 46-68), 50% were female, 22% had ISS stage 3 & 50% had high-risk FISH. Induction therapy was VRD in 7 and daratumumab + VRD in 3 patients; median induction duration: 4 months (3-6) & median lenalidomide exposure: 6 cycles (4-6), with > VGPR in 70%. Median total stem cell yield (CD34+ cells/kg x 106) was 7.1 (3-16.2), day 1 yield was 5.4 (1.1-16.2) & yield per apheresis session was 4 (1.1-16.2). 100% of patients met the primary endpoint of collecting sufficient HSCs in < 2 days of mobilization + apheresis to proceed to transplant (2 x 106 CD34+ cells/kg). Secondary endpoints of 4 and 6 x 106 CD34+ cells/kg in < 2 days were met in 90% & 80% patients. 30% patients underwent 1 apheresis, while 70% underwent 2 sessions. MGTA-145 was well tolerated. At least 1 adverse event (AE) was seen in 90% of patients, 20% had grade 2 AEs (anemia, hypokalemia) and 20% had grade 3 AEs (worsening of baseline grade 3 anemia; hypocalcemia); all resolved. Acute & transient bone pain was seen in 40% of patients (back-2, hip-1, sternum-1), all grade 1, all on day 1, & resolved without intervention after 6 minutes (3-10). All 6 patients in the safety cohort have completed transplant with melphalan 200 mg/m2. Median of 4.1 (3.4-5.6) x 106 CD34+ cells/kg were infused. All patients have engrafted timely (DiPersio Blood 2009); median time to neutrophil engraftment: 12 days (11-13) & platelet engraftment: 17 days (16-19). Apheresis graft analysis is available in these 6 patients. Grafts with MGTA-145+plerixafor showed high enrichment for CD90+CD45RA- among CD34+ cells, a CD34 subset of long term engrafting HSCs (median: 31% of CD34+ cells, 27-52), higher than seen with G-CSF (6%, Goncalves TCT 2021). 67% of grafts were minimal residual disease negative with next generation flow cytometry. Conclusions: This is the first study to evaluate the novel regimen of MGTA-145 + plerixafor for same day stem cell mobilization & collection in myeloma/hematologic malignancies, with 100% efficacy in interim analysis and the first to demonstrate successful engraftment in patients with cells collected with this GCSF free regimen. Clinical trial information: NCT04552743.

Abstract Patients with immunoglobulin M (IgM) light chain (AL) amyloidosis have a distinct clinical presentation compared with those with non-IgM amyloidosis. We hypothesized that differential immunoglobulin light-chain variable region (IGVL) gene usage may explain the differences in organ involvement, because IGVL usage correlates with organ tropism. IGVL usage was evaluated by mass spectrometry of amyloid deposits (IgM, n = 45; non-IgM, n = 391) and differed across the 2 groups. In the λ family, LV2-08 (13% vs 2%; P &lt; .001) and LV2-14 (36% vs 10%; P &lt; .001) usage was more common in IgM vs non-IgM amyloidosis, whereas LV1-44 (0% vs 10%; P = .02) and LV6-57 (2% vs 18%; P = .004) usage was less common. In the κ family, there was a trend toward higher KV4-01 (11% vs 4%; P = .06) usage in IgM amyloidosis. IGVL usage correlated with disease characteristics/organ tropism. LV2-14 (more common in IgM amyloidosis) has historically been associated with peripheral nerve involvement and lower light chain burden, which were more frequent in IgM amyloidosis. LV1-44 (less common in IgM), associated with cardiac involvement, was less frequent in IgM patients. LV6-57 (less common in IgM) is associated with t(11;14), which was less frequent in IgM patients. In conclusion, IGVL gene usage differs in patients with IgM vs non-IgM amyloidosis and may explain the distinct clinical presentation.

AbstractThree sets of criteria (International Society of Amyloidosis [ISA], Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only the Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio [HR] 2.8 [95% CI: 1.5–5.3, p = .001] and 2.5 [CI: 1.4–4.6, p = .004, respectively]), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 [95% CI: 0.17–0.84], p = .017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post‐treatment, the Kastritis criteria performed better for response 3 months after treatment. All three sets of criteria performed well at and after 6 months post‐treatment. These differences are important when choosing endpoints for clinical trials.

AbstractInduction therapy for multiple myeloma with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (d) (VRd) was traditionally administered as bortezomib given twice weekly on a 3 week cycle. A modified schedule of weekly bortezomib has been adopted over time to decrease treatment burden for patients and reduce treatment‐emergent neuropathy. This study evaluates the response rates and outcomes with different schedules of bortezomib in VRd administered for first‐line treatment for patients with newly diagnosed MM (NDMM). We retrospectively analyzed patients treated with upfront VRd from June 30th 2008 to December 31st 2018, for variations of bortezomib administration. Five hundred and fifty‐five (555) NDMM patients met inclusion criteria; median age 63 years and 61% men. Bortezomib was administered twice weekly every 21 days in 43%, once weekly every 21 days in 41% and once weekly every 28 days in 16%. Though peripheral sensory neuropathy was more frequent with twice weekly dosing (P = .002), this group achieved shorter time to best response (P = .01). Weekly every 21‐day treatment saw higher VGPR or better rates (P = .02). However, with median follow up time of 37 months (IQR 22–56), we found no difference in PFS or OS among the groups. While small differences in response rates were found among the varying administration schedules of bortezomib administration, there was no significant effect on PFS or OS. Given that VRd remains a first line standard of care option for newly diagnosed MM, in the absence of a large trial comparing bortezomib dosing schedule modifications, these results are helpful in supporting current practices of once weekly administration.

Introduction: With the expanding use of CAR-T cell therapy, which is associated with serious adverse effects (AEs), there is a need to characterize the patient's experience over time to guide patient/provider education, and help optimize symptom management. This study reports on longitudinal evaluation of patient-reported quality of life (QOL) and symptom burden of CAR-T cell therapy compared with established forms of cellular therapy i.e autologous stem cell transplant (autoSCT) and allogeneic SCT (alloSCT). Methods: Patients with hematologic malignancies were prospectively recruited in three cohorts: CAR-T, autoSCT and alloSCT. The primary endpoint was change in QOL from baseline, using the FACT-G questionnaire. Secondary endpoints were patient-reported AEs (PRO-AEs) using 7 items from the PRO-CTCAE and assessment of cognition/memory using the NeuroQOLv2 questionnaire. PRO-CTCAE data was graded using a composite score (combining frequency, severity, and interference) and rates, using a method adjusting for pre-existing baseline symptoms, were compared using Fisher's exact test. We also evaluated the time profile of PRO-AEs using the Toxicity over Time (ToxT) approach, a longitudinal approach to AE analysis (Thanarajasingam Lancet Onc 2016). Patients completed questionnaires at baseline, week 2 and monthly thereafter. Results: From 07/2018 to 06/2019, 93 patients were recruited (CAR-T: 20; autoSCT: 37; alloSCT: 36). At data cut-off, week 2 and months 1, 2 and 3 data were available in 74, 62, 46 and 35 patients, respectively. There was no difference in patient age across the 3 groups (median age 63, range 23-77; p=0.26). Baseline QOL by FACT-G total score (mean=83.4, SD=14.7; p=0.77), side effect bother by FACT-G GP5 (66/93 [71%] a little bit or less; p=0.72), activities and function (70/93 [75%] fairly normal activities or no limitations; p=0.68) and cognition by NeuroQOL t-score (mean=52.2, SD=8.13; p=0.39) were similar across 3 groups at baseline. The CAR-T group experienced significantly less worsening in QOL (FACT-G) than both autoSCT and alloSCT groups (Fig. 1a). Worsening in overall QOL nadired at week 2, after which QOL gradually returned to baseline in all groups. When comparing changes from baseline in overall QOL, statistically significant differences between groups were evident at week 2 (CAR-T vs autoSCT p&lt;0.001; vs alloSCT p&lt;0.001), month 1 (CAR-T vs autoSCT p=0.02; vs alloSCT p=0.003), month 2 (CAR-T vs autoSCT p=0.02; vs alloSCT p=0.001) and month 3 (CAR-T vs autoSCT p=NS; vs alloSCT p=0.03). Results for physical (Fig. 1b) and functional well-being (WB) were similar, with significantly less QOL worsening at week 2 in CAR-T vs autoSCT and alloSCT groups. The most common PRO-AEs (Table 1) in the CAR-T group were decreased appetite (59%), diarrhea (53%) and fatigue (44%). There was no statistically significant difference in the PRO-AEs between CAR-T and autoSCT groups. However, patients undergoing alloSCT had significantly higher proportion of PRO-AEs vs the CAR-T group, except for neuropathy and sad feelings. AutoSCT and alloSCT groups had significant worsening of FACT-G side effect bother (GP5) at week 2, which was significantly different from that of the CAR-T group, following which the side effect bother gradually returned to baseline. (Fig. 1c) This was the first application of ToxT to PRO-CTCAE data (graphs not shown). Bar charts of maximum grade frequency and stream plots of mean grade over time demonstrate that mouth sores, fatigue, diarrhea and decreased appetite peak at week 2 and improve by month 3, and are of lesser severity in the CAR-T vs autoSCT and alloSCT groups. The trajectory of maximum grade across all PRO-AEs was similar by group as overall side effect burden by FACT-G GP5. Heatmap visualization demonstrated significant intra-patient variability and allowed inspection of data completeness. No difference in cognition and memory was observed across the three groups over the first three months. (Fig. 1d) Conclusion: This study is the first to our knowledge to provide comprehensive PRO data comparing QOL, patient-reported AEs and cognition in CAR-T cell therapy vs. auto- and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional WB domains was better in the CAR-T group vs. SCT groups. These data can serve as a guide for patient education and symptom management in CAR-T cell therapy. Co-senior authors: SKK & ACD Disclosures Paludo: Celgene: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding. Gertz:Johnson and Johnson: Speakers Bureau; Celgene: Consultancy; Appellis: Consultancy; Amyloidosis Foundation: Research Funding; DAVA oncology: Speakers Bureau; Physicians Education Resource: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Teva: Speakers Bureau; Research to Practice: Consultancy; Annexon: Consultancy; Alnylam: Consultancy; International Waldenstrom Foundation: Research Funding; Ionis/Akcea: Consultancy; Spectrum: Consultancy, Research Funding; i3Health: Other: Development of educational programs and materials; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Springer Publishing: Patents & Royalties. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Ansell:Trillium: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding. Bennani:Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

AbstractWe evaluated bone marrow minimal residual disease (MRD) negativity in 44 patients with light chain (AL) amyloidosis using next generation flow cytometry (sensitivity ≥1 × 10−5; median events analyzed: 8.7 million, range: 4.8 to 9.7 million). All patients underwent MRD testing in 2 years from start of therapy (median: 7 months). The overall MRD negative rate was 64% (n = 28). The MRD‐negative rate after one‐line of therapy was 71% (20/28). And, MRD negative rates were higher with stem‐cell transplant as first‐line therapy (86%, 18/21) vs chemotherapy alone as first‐line treatment (29%, 2/7), P = .005. The MRD negative rate amongst patients in complete response was 75% (15/20), and in very good partial response, 50% (11/22). There were two patients in partial response/rising light chains (with renal dysfunction) who were MRD negative. There were no differences in baseline characteristics of MRD negative vs MRD positive patients, except younger age amongst MRD‐negative patients. Patients with MRD negativity were more likely to have achieved cardiac response at the time of MRD assessment, 67% (8/12) vs 22% (2/7), P = .04. Renal response rates were similar in both groups. Progression free survival was assessed in the 42 patients achieving CR or VGPR. After median follow‐up of 14 months, the estimated 1‐year progression free survival in MRD negative vs MRD positive patients was 100% (26 patients, 0 events) vs 64% (16 patients, five events), P = .006, respectively. MRD assessment should be explored as a surrogate endpoint in clinical trials and MRD risk‐adapted trials may help optimize treatment in AL amyloidosis.

Introduction: The clinical presentation and frequency of organ involvement are quite distinct in patients with IgM amyloidosis compared to patients with non-IgM amyloidosis, with less heart involvement and more nerve, soft tissue and lung involvement in IgM patients. It has been observed that immunoglobulin light chain variable region (IGVL) gene and gene family of the plasma cell clone impact phenotypic manifestations in AL amyloidosis, particularly organ tropism. (Kourelis et al. Blood. 2017;129). Given the variability in clinical features amongst patients with IgM vs. non IgM AL amyloidosis, we hypothesized that IGVL gene usage would be different between these two groups. Methods: Patients with newly diagnosed IgM and non-IgM amyloidosis seen at our institution from 01/2006 to 12/2015 were identified. IGVL gene usage was assessed by liquid chromatography tandem mass spectrometry (LC/MS/MS) as previously described. (Vrana et al Blood 2009;Dasari et al J of Proteome Res; Kourelis et al. Blood. 2017). Mass spectrometry data for IGVL analysis was obtained from clinically available data. LC/MS/MS was performed on available archival specimens when such data was not available clinically. Results: Patients with newly diagnosed amyloidosis who had sufficient mass spectrometry data on fat aspirate or tissue biopsy for IGVL gene usage identification were included (IgM AL, N=44 and Non-IgM AL, N=391). Clinical Features: As expected, differences were noted in baseline characteristics of patients with IgM vs. non-IgM AL amyloidosis. Patients with IgM amyloidosis were older (68 vs. 64 years, p=0.04) and more likely to have kappa as the involved light chain (34% vs. 25%, p=0.2), though the difference did not reach statistical significance. IgM amyloidosis patients had lower difference in involved and uninvolved free light chains (dFLC) (15.5 vs. 25.8 mg/dL, p=0.01) and lower NTProBNP levels (median: 1987 vs. 2655 pg/mL, p=0.02) compared with non-IgM amyloid patients. Presence of t(11;14) was less common by FISH (30% vs. 48%, p=0.1), though the difference did not reach statistical significance. Patterns of organ involvement were different, with heart involvement being less frequent in IgM patients (64% vs. 76%), while peripheral nerve (30% vs. 18%, p=0.05), soft tissue (41% vs. 21%, p=0.005) and lung involvement (7% vs. 3%, p=0.1) were more common in patients with IgM vs. non-IgM AL amyloidosis. There was no difference in liver (9% vs. 15%), kidney (50% vs. 51%) GI (23% vs. 25%) or autonomic nervous system involvement (18% vs. 14%). IGVL Gene Usage: As shown in Figure 1, IGVL usage differed across the two groups. In the lambda group, LV2-08 (14% vs. 2%, p<0.001) and LV2-14 (36% vs. 10%, p<0.001) were more common in IgM amyloid patients, while LV1-44 (0% vs. 10%, p=0.02) and LV6-57 (2% vs. 18%, p=0.004) were less common in the IgM group. There was also a trend towards less frequent involvement of LV3-01 (2% vs. 12%, p=0.07) in IgM amyloid patients. In the kappa group, KV4-01 (11% vs. 4%, p=0.04) was more common in patients with IgM amyloidosis. Correlation Between IGVL Gene usage and Clinical Features: IGVL gene usage correlated with disease characteristics and differences in the clinical presentation of patients across the two groups. LV2-14 was more commonly seen in IgM amyloid patients (above). It has been previously associated with a higher frequency of peripheral nerve involvement (Kourelis et al. Blood 2017), which was more frequent in IgM group. LV2-14 is also associated with low dFLC levels, which were noted to be lower in the IgM AL cohort. LV1-44 has been associated with higher likelihood of cardiac involvement. LV1-44 was seen less frequently in the IgM amyloid patients, who also had lower rates of cardiac involvement. LV6-57 has been historically associated with higher rates of t(11;14). It was less common in IgM AL patients, who also had lower rates of t(11;14). Conclusions: IGVL gene usage differed significantly in patients with IgM vs. non-IgM amyloidosis, correlating with differences in disease characteristics and organ involvement. This is the first study to our knowledge to report IGVL gene usage differences in IgM vs. non-IgM AL amyloidosis. Differences in IGVL gene usage may explain the distinct clinical presentation seen in IgM amyloidosis, the biology of which has so far remained poorly understood. *SS and SD contributed equally Disclosures Dasari: The Binding Site: Patents & Royalties: US Patent Rights on Mass Spectroscopy Licensing agreement with The Binding Site, Research Funding. Dispenzieri:Alnylam: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Akcea: Consultancy; Intellia: Consultancy. Murray:The Binding Site: Patents & Royalties: US Patent Rights on Mass Spectroscopy Licensing agreement with The Binding Site, Research Funding. Kumar:Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Research Funding. Gertz:Prothena: Honoraria; Alnylam: Honoraria; Ionis: Honoraria; Janssen: Honoraria; Spectrum: Honoraria, Research Funding; Celgene: Honoraria.

Introduction: Primary cold agglutinin disease (CAD) is a rare disorder and accounts for 15% of all autoimmune hemolytic anemia. It is associated with an underlying monoclonal protein, which is IgM kappa in the majority of patients. The IgM protein triggers complement mediated extravascular hemolysis. The underlying pathophysiology by which autoimmune hemolysis affects only a small subset of patients with IgM monoclonal protein is poorly understood. Changes in the IgM structure via post-translational modifications of light chains (LCs), such as glycosylation are enriched in patients with AL amyloidosis, another rare disorder where disease manifestations are driven by the protein structure. (Kumar S et al Leukemia 2017). We hypothesized that presence of post-translational glycosylation is a potential mechanism allowing the IgM protein to trigger complement mediated hemolysis in CAD. Methods: Serum samples of patients being evaluated for monoclonal protein disorders were analyzed by immuno-enrichment-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX. Patients who had an underlying IgM monoclonal protein identified by MASS-FIX from 07/23/2018 to 5/14/2019 were included this study. Glycosylated LCs were identified by the shift in their molecular mass due to the added molecular mass of the carbohydrates. Glycosylation was compared in patients with IgM associated CAD vs. other IgM disorders. Results: 438 unique patients with an IgM monoclonal protein identified on MASS-FIX were included in the study. CAD was present in 3% (n=14) of patients. The primary underlying diagnosis in the remaining patients was monoclonal gammopathy of undetermined significance (MGUS): 47% (n=206), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM): 30% (n=132), non-LPL lymphoma: 6% (n=28), AL amyloidosis: 4% (n=19), CLL: 4% (n=18), cryoglobulinemia: 2% (n=10), multiple myeloma: 2% (n=9) and other: 0.5% (n=2) Glycosylation was present in 7% (31/438) of patients in this cohort. Glycosylation was significantly more prevalent in patients with CAD than other IgM gammopathies (64% vs. 5%, p &lt;0.001). CAD was present in 29% of patients with glycosylation and in only 1% of patients without glycosylation, p&lt;0.001. Disease characteristics of patients with CAD, including patients with and without glycosylated LCs are listed in Table 1. No statistically significant differences were observed in the features of CAD patients with and without glycosylation, though sample size was small. All patients (100%) had IgM kappa monoclonal protein. Median M-spike was 0.5 g/dL. The associated disorder was IgM MGUS in 50% of patients, LPL/WM in 29%, marginal zone lymphoma in 14% and a non-specific B-cell lymphoproliferative disorder in 7% of patients. Median hemoglobin was 11.2 g/dL. All patients had characteristic RBC agglutination on peripheral smear. Elevated LDH and undetectable haptoglobin were seen in 100% of patients. Cold agglutinin titer was positive (&gt;1:64) in 12 of 13 patients (85%) in whom it was tested. The remaining patient had a titer of 1:8. Polyspecific Coombs test/direct antiglobin test (DAT) was positive in 100% of patients (n=12 tested) and all patients who were tested with monospecific DAT had an antiC3 antibody (n=10). One patient also had monospecific anti IgG antibody. Transfusions were needed in 21% of patients. Other clinical manifestations included acrocyanosis in 43% (n=6) and Raynaud's phenomenon in 50% (n=7) of patients, respectively. Treatment for CAD included rituximab with or without steroids in 50% (n=7) of patients, rituximab-based chemotherapy in 29% (n=4) of patients, with observation alone in 21% (n=3) of patients. Conclusions: Modification of the IgM immunoglobulin structure by post-translational glycosylation of LCs was significantly more common in patients with CAD compared with other IgM monoclonal gammopathies (64% vs. 5%, p &lt;0.001). CAD was seen in only 1% of patients without glycosylation, while one-third of patients with glycosylation had CAD. This is a novel finding. As MASS FIX is now routinely done for detection of monoclonal proteins at our institution, the presence of LC glycosylation can provide diagnostic clues and can be a potential therapeutic target in the future. Future studies in larger, independent cohorts of patients are needed to confirm these findings. *SS & DLM contributed equally Disclosures Murray: The Binding Site: Patents & Royalties: US Patent Rights on Mass Spectroscopy Licensing agreement with The Binding Site, Research Funding. Dasari:The Binding Site: Patents & Royalties: US Patent Rights on Mass Spectroscopy Licensing agreement with The Binding Site, Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Dispenzieri:Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding; Intellia: Consultancy; Akcea: Consultancy. Gertz:Spectrum: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Prothena: Honoraria; Ionis: Honoraria; Alnylam: Honoraria.

AbstractThe role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post‐transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression‐free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression‐free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression‐free survival for patients who achieve less than very good partial response.