Citations

e20000 Background: In the novel agents’ era, refractoriness to induction in Multiple Myeloma (MM) is relatively rare. This population remain an unmet need and are often excluded from clinical trials. In the current era, chemotherapy-induced stem cell collections are used at Mayo Clinic in “poor responders” to induction, such as patients that progress prior to ASCT or patients with significant disease burden after induction. Methods: This is a retrospective study that includes all MM patients the underwent chemo-mobilization between January 2012 and September 2020 at Mayo Clinic. We compared our cohort to a cohort of 125 matched patients that were transplanted over the same time period and underwent mobilization with G-CSF and “on-demand” plerixafor. We matched the cohorts by level of response by IMWG at pre-transplant evaluation. Results: 125 newly diagnosed MM patients who received novel agents’ induction and had a poor response to induction were mobilized using IV intermediate-dose cyclophosphamide (83%) or VDT-PACE (17%) plus G-CSF and “on-demand” plerixafor. The median PFS and OS of the chemo-mobilized cohort were 16 months (95% CI 11-20) and 47 months (95% CI 37-71), respectively. Patients receiving chemo-mobilization had higher stem cell yields than the growth factor only cohort (median 9.88X106 cells/kg versus median 8.77X106 cells/kg, respectively (P<0.001)). The safety profile of chemo-mobilization was favorable, with no difference between the two groups in length of hospitalization during ASCT (P=0.95), days to neutrophil or platelet engraftment, and risk of bacteremia (P=0.38). 29% of the chemo-mobilized cohort and 66% of the matched cohort required plerixafor for adequate mobilization (P<0.001). Conclusions: Chemo-mobilization enhances stem cell collection in MM patients with a suboptimal response to induction and reduces the need for plerixafor without adversely impacting the post-transplant clinical course. [Table: see text]

8030 Background: CARTITUDE-1 is a single arm study of Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) anti-BCMA CAR-T cell therapy in US patients (pts) with relapsed multiple myeloma (RRMM) refractory to both IMiD and proteasome inhibitor (PI) or with at least 3 prior lines of therapy and previously exposed to anti-CD38 monoclonal antibody (MoAb). While recently reported efficacy results of cilta-cel were encouraging, it is unknown how they compare with similar pts receiving conventional (non CAR-T) treatment. Methods: We utilized a contemporary US-based dataset of pts with MM refractory to anti-CD38 MoAb (MAMMOTH) to identify pts who would meet eligibility for CARTITUDE-1 and who received conventional therapy. We analyzed the intent-to-treat population (ITT) in CARTITUDE-1, defined as pts who underwent apheresis (N=113) and a modified ITT population (mITT) defined as subset of pts who received cilta-cel at the RP2D (N=97). From the MAMMOTH dataset, we identified a population corresponding to CARTITUDE-1 ITT (N=190) and a mITT population, pts without death or progression within 47 days (median time between apheresis and cilta-cel infusion) from onset of therapy (N=122). We calculated propensity scores (PS) with demographics, N of prior therapies, cytogenetics and refractoriness to MM agents as covariates. An analyst blinded to outcomes performed nearest neighbor 1:1 PS matching. We analyzed overall response rate (ORR), progression-free (PFS) and overall survival (OS) for ITT and mITT in CARTITUDE-1 vs matching MAMMOTH cohorts. Results: Ninety-five ITT (75 received bridging therapy, 82 received cilta-cel) and 69 mITT (54 received bridging) CARTITUDE-1 pts matched MAMMOTH pts (Table). Among the pts in the MAMMOTH ITT cohort 34% received pomalidomide, 24% anti-CD38 MoAb, 19% carfilzomib and 35% cytotoxic chemotherapy in next therapy. ORR in the ITT cohorts was higher in CARTITUDE-1 (84% vs. 28%). Compared to their MAMMOTH counterparts, pts in CARTITUDE-1 ITT cohort had improved PFS (12 mo. 73% vs. 12%) and OS (12 mo. 83% vs 39%). Between the mITT cohorts, CARTITUDE-1 pts had superior ORR (96% vs. 30%), PFS (12 mo 79% vs. 15%) and OS (12 mo. 88% vs. 41%). Conclusions: In pts with RRMM beyond therapy with IMID, PI, and anti-CD38 MoAb, treatment with cilta-cel is associated with higher response rate and superior PFS and OS when compared to conventional treatment.[Table: see text]

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.

8022 Background: Maintenance therapy in multiple myeloma (MM) after first autologous hematopoietic cell transplantation (AHCT1) is considered standard of care. Data regarding maintenance therapy after a salvage AHCT (AHCT2) in the setting of relapsed MM are scarce. Therefore, we used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to examine the use of maintenance therapy after AHCT2 in MM patients and its effect on post-transplant patient outcomes. Methods: We included US adult MM patients who underwent AHCT2 after melphalan conditioning regimen from 2010-2018, and excluded patients who underwent tandem transplants. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Cox proportional hazards models were developed to study the main effect (maintenance use) with other covariates of interest including age, sex, race, performance status, HCT-comorbidity index, MM subtype, stage, creatinine, cytogenetic, conditioning melphalan dose, disease status at transplant, and time from AHCT1 to AHCT2. Results: Of 522 patients, 342 received maintenance therapy and 180 did not after AHCT2. Baseline characteristics were similar between the two groups. Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Common maintenance regimens included immunomodulatory drugs (IMID)-lenalidomide (N = 145, 42%) or pomalidomide (N = 46, 13%) and proteasome inhibitor, bortezomib (N = 45, 13%). Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, p < 0.001, REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)%, p 0.003, PFS 27.8% (22.4-33.5) vs. 9.8% (5.5-15.2), p < 0.001, and OS 54% (47.5-60.5) vs 30.9% (23.2-39.2) p < 0.001, respectively. IMID-containing maintenance regimens were associated with an improved 5-year PFS and OS compared to other maintenance regimens. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis, including NRM: hazard ratio (HR) 0.19 (0.08-0.44), p 0.0001, REL: HR 0.58 (0.47-0.72), p < 0.0001, PFS HR 0.52 (0.43-0.64), p < 0.0001, and OS HR 0.46 (0.36-0.60), p < 0.0001. We conducted additional analyses to investigate a possible selection bias in the maintenance group including landmark analysis at 100-days and 6-months post-AHCT2 as well as a subgroup analysis of patients who received melphalan 200mg/m2 as conditioning for AHCT2 (as a surrogate for fitness)- all these analyses also showed improved outcomes in the maintenance group. Second cancers were reported in 17 (5%) patients in the maintenance group and 6 (3%) patients and no-maintenance group (p 0.39). Conclusions: Maintenance therapy after AHCT2 is associated with superior outcomes in MM patients.

8020 Background: MM patients (pts) often receive several lines of therapy with multiple drug combinations and, as lenalidomide (R)-containing regimens are commonly used as first-line therapy, R-free options for subsequent lines are necessary. Additionally, as pts age and become less tolerant to treatment, more convenient regimens, such as all-oral options, with less toxicity are needed. Dexamethasone (dex)-based doublets are effective and tolerable in this setting. Methods: Proteasome inhibitor (PI)-exposed and/or intolerant and R-refractory pts who had ≥2 prior therapies (N = 122) were randomized 3:2 to receive: ixazomib (ixa) 4 mg (5.5 mg from cycle 2 if tolerated) on day (d) 1, 8, 15, and dex 20 mg (≥75 years [yrs], 10 mg) on d 1, 2, 8, 9, 15, 16, 22, 23; or pomalidomide (pom) 4 mg on d 1–21, and dex 40 mg (≥75 yrs, 20 mg) on d 1, 8, 15, 22, in 28-d cycles until progressive disease (PD) or unacceptable toxicity. Pts were stratified by age ( < 65 vs ≥65 yrs), International Staging System (ISS) disease stage at study entry (I/II vs III), and prior lines of therapy (2 vs ≥3). The study was powered to test the primary endpoint of progression-free survival (PFS). Results: In the ixa-dex (n = 73) vs pom-dex (n = 49) arms, median age was 72 vs 68 yrs (36% vs 18% ≥75 yrs), 25% vs 22% of pts had ISS stage III MM, and 52% vs 53% had received ≥3 prior therapies (per stratification). At data cutoff (5/31/2020), 19% vs 20% of pts were ongoing on treatment with ixa-dex vs pom-dex; primary reasons for discontinuation were PD (47% vs 57%) and adverse events (AEs; 23% vs 12%). With median follow-up of 15.3 vs 17.3 months (mos), median PFS (mPFS) was 7.1 vs 4.8 mos with ixa-dex vs pom-dex (hazard ratio [HR] 0.847; 95% confidence interval [CI] 0.535–1.341; p = 0.477); the Table shows mPFS by prior lines, and secondary endpoints. Pts received a median of 6 cycles with both ixa-dex (range 1–25) and pom-dex (range 1–27); 64% of ixa-dex pts were able to escalate to a 5.5 mg dose of ixa. 69% vs 81% of ixa-dex vs pom-dex pts had grade (G) ≥3 AEs, 51% vs 53% had serious AEs, 39% vs 36% had an AE leading to drug discontinuation, 44% vs 32% had an AE leading to dose reduction, and 13% vs 13% died on study. Health-related quality of life (HRQoL; EORTC QLQ-C30/MY20, and EQ-5D-5L) was maintained, and similar between arms. Conclusions: Ixa-dex prolonged PFS vs pom-dex in these heavily pretreated, PI-exposed and/or intolerant, R-refractory pts, but the difference was not statistically significant. Ixa-dex was well tolerated, with lower G≥3 AE rates vs pom-dex, and comparable HRQoL. Clinical trial information: NCT03170882.

7554 Background: Chimeric antigen receptor T-cell therapy (CAR-T) are commonly administered inpatient due to concern for early onset cytokine release syndrome (CRS), especially with axicabtagene ciloleucel (axi-cel). We report Mayo Clinic Rochester experience for hospital-based outpatient (HBO) management of patients (pts) receiving axi-cel and identify opportunities for improvement. HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. Lymphodepletion chemotherapy and CAR-T infusion is given on HBO followed by daily monitoring till day 8 and thereafter, as clinically needed until admission criteria is met. Methods: We retrospectively analyzed database of pts who received axi-cel between 1/2018 and 1/2021. After 06/2020, remote patient monitoring (RPM) tools were implemented to collect patient-reported neurologic symptoms and vital signs via bluetooth-enabled devices 4 times daily through month 1. Adverse data trends are addressed by the HBO team. Results: Among 72 recipients, 89% received their cells outpatient; 8% remained outpatient for the entire month. CRS and neurotoxicity incidence were comparable to those reported from CIBMTR. Median time to first admission was 2 days (Table). Use of bridging therapy, increased CRP and LDH were associated with early admission (≤3 days). Median time to tocilizumab, steroid, oxygen support, vasopressor was 4 days after admission. Half of HBO visits required intervention such as blood transfusions, IV medications through the first month. Nine pts had enrolled in RPM to date; with 8 having evaluable data. With 4 scheduled entries/day, a median of 1 entry/day was skipped and 2 entries/day were answered incompletely. An average of 57 additional unscheduled entries were generated per pt. Among a median of 373 (range 91-522) readings per pt over the first month, 4% (2%-20%) of the readings generated alerts. An average of 4 alerts were seen within 48 hours prior to admission. Data including additional subjects will be presented at ASCO meeting. Conclusions: We report a feasible outpatient care model for management of axi-cel recipients with safe outcomes. Clinical characteristics associated with more aggressive disease are associated with likelihood of early admission. Early RPM experience suggest use of digital tools could improve monitoring compliance and may predict evolution to symptoms requiring escalation of care.[Table: see text]

2500 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach for relapsed refractory hematologic malignancies. The Indiana strain of Vesicular Stomatitis Virus was engineered to encode interferon beta (IFNβ) and sodium iodine symporter (NIS) to produce VSV-IFNβ-NIS. Virally encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. NIS was inserted to noninvasively assess viral biodistribution using SPECT/PET imaging. We present the results of the phase 1 clinical trial NCT03017820 of systemic administration of VSV-IFNβ-NIS among patients (pts) with relapsed refractory Multiple Myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML). Methods: VSV-IFNβ-NIS was administered at 5x109 TCID50 (50% tissue culture infectious dose) dose level 1 to dose level 4, 1.7x1011 TCID50. The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Correlative objectives included monitoring viremia and virus shedding. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: 15 pts received VSV-IFNβ-NIS: MM (7), TCL(7) and AML(1); 3 pts were treated at each dose level (DL) 1 through 3 (respectively 0.05, 0.17, and 0.5 x 1011 TCID50), & 6 pts were treated at dose level 4 (1.7x1011 TCID50). There were no dose limiting toxicities. The most frequent grades 3 & 4 AEs were hematologic: lymphopenia (46.6 & 26.6%), neutropenia (13.3% & 6.7%). CRS grades 1 (6.7%) and 2 (46.6%) were the non-hematologic AEs of note; mostly at DL 4. Only 1 pt required transient pressor support. Responses were seen in pts with T cell lymphoma. At DL2, there was a partial response (PR) lasting 3 months in a pt, post 12 prior lines of therapy. At DL4 there was a 6 month PR in a pt with PTCL and another pt with cutaneous relapse of PTCL who enjoys an ongoing CR, more than 1 year post VSV infusion; both pts received 5 prior lines of therapy. Viremia was detected in all pts at the end of infusion only up to 72 hrs post infusion; no infectious virus was recovered in buccal swabs or urine. Neutralizing anti-VSV antibodies were present by day 29. IFN levels were detectable within 30 mins of infusion, peaking between 4 & 48 hrs. TCL pts mounted higher hIFNβ levels within 48 hrs; the pt with CR mounted peak hIFNβ response of 18213.3pg/ml at 48 hrs post infusion, 15-fold higher than any other pt. Conclusions: VSV-IFNβ-NIS can be safely administered by IV infusion among heavily pretreated pts with hematologic malignancies. VSV-IFNβ-NIS as a single agent appears to be most effective at DL4 among patients with TCL, with an ongoing CR in a patient at DL4 more than 1 year post administration. Future trials of combination strategies with immune-modulatory drugs are currently being planned. Clinical trial information: NCT03017820.

Abstract Comparative data guiding initial therapy for Waldenström macroglobulinemia (WM), an infrequently encountered non‐Hodgkin lymphoma, are sparse. We evaluated three commonly used rituximab‐based frontline regimens: rituximab‐bendamustine (R‐Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR) in 220 treatment‐naïve patients with WM, seen at Mayo Clinic between November 1, 2000 and October 31, 2019. The median follow‐up was 4.5 (95%CI: 4–5) years. The R‐Benda cohort (n = 83) demonstrated superior overall response rate (ORR: 98%), in comparison to DRC (n = 92, ORR: 78%) or BDR (n = 45, ORR: 84%) cohorts, p = 0.003. Similarly, longer progression‐free survival (PFS) was evident with R‐Benda use [median 5.2 vs. 4.3 (DRC) and 1.8 years (BDR), p < 0.001]. The time‐to‐next therapy (TTNT) favored R‐Benda [median, not‐reached, 4.4 (DRC) and 2.6 years (BDR), p < 0.001). These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p = 0.77. In a subset analysis of 142 patients genotyped for MYD88 L265P mutation, the ORR, PFS and TTNT were unaffected by the patients' MYD88 signature within each cohort. In conclusion, ORR, PFS and TTNT with R‐Benda are superior compared to DRC or BDR in treatment‐naïve patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88 L265P mutation status.

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.

Abstract Background There is increasing evidence for the clinical benefit of long-term, continuous therapy for NDMM pts. Proteasome inhibitors (PIs) form a backbone of therapy in MM; however, long-term therapy with some PIs may be limited due to toxicity and the need for regular parenteral administration, increasing the treatment burden. Ixazomib, the first oral PI, has been studied in NDMM pts in 4 phase 1/2 studies in which approximately 1 year of induction therapy with once- or twice-weekly ixazomib plus lenalidomide-dexamethasone (IRd), melphalan-prednisone (IMP), or cyclophosphamide-dexamethasone (ICd) was followed by single-agent ixazomib maintenance. Here we report an integrated analysis of pts from these studies who did not undergo autologous stem cell transplant (ASCT) and received ixazomib maintenance therapy. Methods Pts from 4 studies were included: 1) weekly IRd, 12x28-d cycles IRd (weekly ixazomib 1.68-3.95 mg/m² in phase 1, recommended phase 2 dose [RP2D] 4.0 mg; C16005, NCT01217957; ASCT-eligible/-ineligible pts); 2) twice-weekly IRd, 16x21-d cycles IRd (twice-weekly ixazomib 3.0-3.7 mg in phase 1, RP2D 3.0 mg; C16008, NCT01383928; ASCT-eligible/-ineligible pts); 3) IMP, 9x42-d or 13x28-d cycles IMP (weekly/twice-weekly ixazomib 3.0-5.5/3.0-3.7 mg in phase 1, RP2D of weekly ixazomib 4.0 mg; C16006, NCT01335685; ASCT-ineligible pts); 4) ICd, 13x28-d cycles ICd (weekly ixazomib 4.0 mg; C16020, NCT02046070; ASCT-ineligible pts). In all 4 studies, pts completing induction without progressive disease (PD) and, in the IRd studies, not withdrawn for ASCT, could receive single-agent ixazomib maintenance at the last tolerated dose during induction until PD or unacceptable toxicity. Results 121 pts received ixazomib maintenance (25, 18, 35, and 43 in weekly IRd, twice-weekly IRd, IMP, and ICd studies, respectively). Median age was 72 yrs (range 34-90 yrs; 83% aged ≥65 yrs), 62% had IgG myeloma, 47/34/19% had ISS disease stage I/II/III, 40/49% had Eastern Cooperative Oncology Group performance status 0/1. Combined median progression-free survival (PFS) was 33.8 months from time of study entry and 21.4 months from start of maintenance (Figure). Median PFS from the start of maintenance seemed to be longer for the two IRd studies than for IMP, while median PFS for ICd had not yet been reached. 4-yr OS from time of study entry/3-yr OS from the start of maintenance was 82%. Overall response rate was 93% after induction and 94% after maintenance. Best response rate of CR+VGPR after induction was 57% (22% CR), which increased to 63% (35% CR/sCR) after maintenance; 24 pts (20%) improved their response during maintenance (4 pts with CR improved to sCR; 14 VGPR to CR/sCR; 5 partial response [PR] to VGPR/CR; 1 stable disease to PR). Combined mean dose intensity during maintenance was 89.1%. At time of analysis, median duration of maintenance therapy was 2.2 yrs for weekly IRd, 1.0 yr for twice-weekly IRd, and 0.9 yr for IMP and ICd; maximum duration was 4.8, 3.8, 3.9, and 1.6 yrs respectively. 78% of pts had discontinued maintenance, primarily due to PD (55%), and only 7% due to adverse events (AEs). 15% of pts had ixazomib dose reductions during maintenance. Grade ≥3 AEs (48% vs 74%), drug-related grade ≥3 AEs (24% vs 62%), serious AEs (SAEs; 21% vs 43%), and drug-related SAEs (5% vs 19%) were less common during maintenance than during induction. Common grade ≥3 AEs are shown in the Table. Other AEs of clinical interest were also generally similar or less common during maintenance than during induction, including cardiac arrhythmias (13% vs 21%), pneumonia (12% vs 17%), acute renal failure (7% vs 8%), hypotension (4% vs 7%), myocardial infarction (0 vs &lt;1%), and heart failure (2% vs 2%). Only 6 pts (5%) reported a new primary malignancy. There was only 1 on-study death during maintenance, which was not considered related to ixazomib; due to pulmonary edema in an 81-yr old pt with a history of cardiovascular co-morbidities. Conclusions In this integrated analysis, single-agent ixazomib maintenance therapy following an ixazomib-based induction regimen was associated with deepening of responses and good long-term outcomes in NDMM pts not undergoing ASCT. Single-agent ixazomib is feasible for long-term administration, with limited new-onset grade ≥3 AEs. These outcomes appear similar to other studies involving maintenance approaches in NDMM and support the ongoing phase 3 investigation of ixazomib maintenance therapy. Disclosures Dimopoulos: Novartis: Consultancy, Honoraria; Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology; Genesis Pharma: Research Funding. Laubach: Novartis, Takeda, Celgene, Onyx: Research Funding; Novartis, Takeda, Celgene: Consultancy. Hofmeister: Thrassos: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Roche: Research Funding; Karyopharm: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding. San Miguel: Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kumar: Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding; Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Skyline: Honoraria. Lu: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Teng: Array Pharmaceuticals: Equity Ownership; AMAG Pharmaceuticals: Equity Ownership; Gilead Science: Equity Ownership; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Liu: Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Byrne: Oncopeptides AB: Consultancy; Takeda: Consultancy. Berg: Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Labotka: Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. van de Velde: Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Richardson: Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Research Funding; Oncopeptides AB: Membership on an entity's Board of Directors or advisory committees.