Einsele, Hermann

Background: An interim analysis (data cutoff date April 18, 2022) of the international, open-label, phase 3 KarMMa-3 trial (NCT03651128) showed the chimeric antigen receptor T cell therapy idecabtagene vicleucel (ide-cel) significantly improved progression-free survival and treatment response rates, as well as HRQoL, as compared with standard regimens, in patients with triple-class exposed (TCE) RRMM who had received 2-4 prior regimens (Rodriguez-Otero P, et al. N Engl J Med 2023;388:1002-1014; Delforge M, et al., HemaSphere, 2023;7(S3):P905). The aim of the present study was to analyze the effect of ide-cel versus standard regimens (daratumumab [DARA], pomalidomide, and dexamethasone [DEX]; DARA, bortezomib, and DEX; ixazomib, lenalidomide, and DEX; carfilzomib and DEX; or elotuzumab, pomalidomide, and DEX) on HRQoL in KarMMa-3 trial participants with an extended follow-up of patient-reported outcomes (PRO) data collection (data cutoff date April 28, 2023). Methods: In KarMMa-3, HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30), EORTC Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20), and EQ-5D-5L. HRQoL assessments were completed at screening (baseline); the day of ide-cel infusion or the first dose of standard treatment; and monthly from 2 to 28 months; and every 3 months thereafter. The prespecified primary outcomes of interest were EORTC QLQ-C30 global health status/QoL, physical functioning, cognitive functioning, fatigue, and pain; EORTC QLQ-MY20 disease symptoms and side effects of treatment; and the EQ-5D visual analog scale (EQ-VAS). Least squares (LS) mean changes from baseline through month 25 for ide-cel and standard regimens were compared by constrained longitudinal data analysis (cLDA). Effect sizes were estimated by Hedges' g. The effect of ide-cel versus standard regimens on time to confirmed improvement and deterioration in HRQoL (defined by prespecified change thresholds and sustained duration) were compared by stratified Cox proportional hazards regression. There was no adjustment for multiple testing, and all P values reported are nominal. Results: Overall, 254 patients were randomized to the ide-cel arm and 132 to the standard regimens arm. Baseline characteristics were well balanced across treatment arms; both arms had a median age of 63 years, a median of 3 prior anti-myeloma regimens, and median time from MM diagnosis to screening was 4 years. The baseline HRQoL scores were generally comparable between treatment arms. Overall LS mean changes from baseline to month 25 showed significant differences (nominal P value < 0.05) in favor of ide-cel for 18 out of 21 HRQoL domains, with effect sizes (Hedges' g) of 0.27 to 0.82 (Table). For 13 of these domains (including 6 primary domains of interest), the difference in overall LS mean change from baseline exceeded the prespecified minimum important difference (MID) threshold. Time to confirmed improvement was significantly shorter in the ide-cel arm than the standard regimens arm for 19 domains, including all primary domains of interest (Table). Time to confirmed deterioration showed trends of being longer in the ide-cel arm than the standard regimens arm for most domains and was significantly longer for emotional functioning, cognitive functioning, social functioning, dyspnea, and constipation as measured by the EORTC QLQ-C30. The time to confirmed deterioration in side effects of treatment (based on the EORTC QLQ-MY20) was significantly longer for patients in the ide-cel arm and time to confirmed improvement was significantly faster, as compared with the standard regimens arm (Table). Conclusions: In the KarMMa-3 trial, patients with TCE RRMM who had received 2-4 prior regimens, ide-cel significantly and meaningfully improved MM-relevant symptoms, functioning, and overall health status/HRQoL compared with standard regimens. Confirmed HRQoL improvements in the ide-cel arm occurred sooner than standard regimens. PRO improvements were sustained over more than 2 years, which is notable after a single infusion treatment with ide-cel. These patient-reported findings further support the benefit of ide-cel in this patient population.

Background Chimeric antigen receptor (CAR) modified T-cells are leading to a paradigm shift in the treatment of relapsed/refractory (RR) multiple myeloma (MM). A high proportion of patients treated with CAR T-cells, however, experience prolonged cytopenia, with the mechanism remaining poorly understood. Here, we aimed to explore potential biomarkers that might correlate with cytopenia following CAR T-cell therapy in RRMM. Methods We prospectively collected peripheral blood (PB) of RRMM patients treated with idecabtagen-vicleucel (ide-cel) at the following time points: prior to lymphodepleting chemotherapy (LDC) (baseline), after ide-cel on day 4, 7, 14 and 28, and monthly thereafter. Cytopenia was determined according to the CTCAE version 5.0. Flow cytometry was performed with the following markers: CD45, CD3, CD4, CD8, CD62L, CD45RA, CD19, CD14, CD138, CD38 and a BCMA-CAR-detection marker. Results We included 222 PB samples at different sampling time points from 35 RRMM patients, who were pretreated with a median of 5 therapy lines (range 2-10). All patients were triple-class exposed and, 34 (97%) and 9 (26%) patients underwent autologous and allogeneic stem cell transplant (SCT), respectively. First, we analyzed the relationship between baseline parameters and the duration of grade ≥3 cytopenia after ide-cel (n=35). Notably, patients who received allogeneic SCT or >4 lines of therapy did not develop longer lasting cytopenia than the remaining patients. We found a correlation between the baseline hemoglobin level and the duration of grade ≥3 anemia (r=-0.55, P<0.001). Similarly, low baseline platelet count indicated long duration of grade ≥3 thrombocytopenia (r=-0.48, P=0.003). Moreover, high baseline ferritin level correlated with long duration of grade ≥3 anemia (r=0.52, P<0.001) and thrombocytopenia (r=0.51, P=0.002). Furthermore, the maximum ferritin level after ide-cel was an indicator for long lasting grade ≥3 anemia (r=0.73, P<0.001) and thrombocytopenia (r=0.71, P<0.001). Interestingly, we found significant correlations between the duration of grade ≥3 lymphopenia and baseline CD4+ T-cell frequency (r=0.41, P=0.02), CD8+ T-cell frequency (r=-0.38, P=0.04) and CD4+/CD8+ ratio (r=0.4, P=0.03). Noteworthy, patients with β2-microglobulin level >3.5 mg/l displayed longer duration of grade ≥3 anemia (median: 9 vs 0 day, P=0.007) and neutropenia (median: 43 vs 12 days, P=0.02) compared with the remaining patients, suggesting that high tumor load might be a risk factor for prolonged cytopenia after ide-cel. Second, we divided the follow-up PB samples (n=187) into two groups: early (<d60) and prolonged (≥d60) cytopenia to account for direct toxic effects related to LDC. A high ferritin level was associated with low hemoglobin level (<d60: r=-0.45, P<0.001, ≥d60: r=-0.62, P<0.001) and low platelet count (<d60: r=-0.58, P<0.001, ≥d60: r=-0.81, P<0.001) in both groups. In prolonged cytopenia (≥d60), lymphocyte count correlated with the T-cell count (r=0.7, P<0.001), suggesting that prolonged lymphopenia was mainly attributed to the reduced T-cell count after ide-cel. Of note, the frequency of naïve CD4+ T-cells (CD3+CD4+CD62L+CD45RA+) positively correlated with neutrophil count (r=0.58, P<0.001), hemoglobin level (r=0.37, P=0.03) and white blood cell count (r=0.5, P=0.002) in the ≥d60 group, suggesting that delayed immune reconstruction with reduced naïve CD4+ T-cells might contribute to prolonged cytopenia after ide-cel. Moreover, in the ≥d60 group, lymphocyte count was related with the frequency of CAR+CD4+ (r=-0.58, P<0.001), CAR+CD8+ (r=0.58, P<0.001), CAR-CD4+ (r=-0.72, P<0.001), CAR-CD8+ (r=0.75, P<0.001) T-cells, as well as the ratios of CAR+CD8+/CAR+CD4+ (r=-0.6, P<0.001) and CAR-CD8+/CAR-CD4+ (r=-0.75, P<0.001). Conclusion Here, we present one of the first prospective studies investigating the factors associated with prolonged cytopenia after CAR T-cell therapy in RRMM. High tumor load, preexisting cytopenia and high ferritin level are related with prolonged cytopenia after ide-cel. Delayed immune reconstruction, characterized by reduced naïve CD4+ T-cell count, indicates prolonged cytopenia following ide-cel therapy. Patients with high CD4+/CD8+ ratio are at risk of prolonged lymphopenia (with reduced T-cell count), which may be a risk factor for infectious complications and an issue for subsequent T-cell based immunotherapies.

Introduction: BCMA-directed CAR-T and Bispecific T-cell engager (BiTE) therapies have shown remarkable overall response rates in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). This has led to the approval of idecabtagene vicleucel, ciltacabtagene autoleucel and teclistamab by the FDA, EMA and other regulatory agencies. We performed a global survey on accessibility, practice patterns, and toxicity management of commercially available CAR-T and BiTE therapies. Methods: An online survey was completed by clinicians attending the International Myeloma Society's Immune Effector Cell Therapies in Multiple Myeloma Workshop, in-person or virtually, made available for 30 days after the meeting held in March 2023, Boston, MA. Results: 87 clinicians from 16 countries completed the survey, most practicing in an academic practice (86%) and in an urban environment (89%). Sixty-four percent of the respondents practice in North America followed by Europe (25.3%) including Germany, United Kingdom, Ireland, Italy, Netherlands, Spain, France, Greece, and Cyprus, and 6.9% from Asia and 3.4% from Australia. Seventy-seven percent reported CAR-T cell therapy was approved in their country with 44.8% treating 1-5 patients and 14.9% treating >5 patients per month; 67% reported BiTE therapy was approved in their country with 14.9% treating >5 patients per month. Of evaluable responses (n = 40), 62% administered CAR-T therapy inpatient and 15% administered CAR-T therapy outpatient ≥ 50% of the time. Length of time between decision to treat with CAR-T therapy to infusion was 6-12 weeks for 42% of responders and <6 weeks for only 20%. Most (75%) reported inpatient administration of BiTE therapy step-up dosing; 17.5% reported outpatient step-up dosing administered ≥ 50% of the time. Use of institutional or practice SOPs for CAR-T and BiTE therapy patient selection was reported by 85% and 58%, respectively, with the factors influencing SOP outlined in Table 1. Of available CAR-T therapies, 53% prefer cilta-cel and 23% reported CAR-T therapy preference depended most on patients' co-morbidities/frailty (89%), timing of next available apheresis (67%), age (56%), CNS disease (44%) and other factors. Maintenance therapy after CAR-T therapy was reportedly used by 25% and 5% of respondents in 1-10% and 11-50% of their patients, respectively, to “maintain level of response achieved” (50%) or “achieve a deeper level of response” (25%). About half (43%) of the respondents reported using an SOP or particular criteria for secondary Hemophagocytic Lympho-Histiocytosis/Macrophage Activation Syndrome/CAR-related-HLH (sHLH/MAS/CarHLH) management that varied between the use of ASTCT Working Group IEC associated HLH-like syndrome Criteria (47%) (Hines 2023), CARTOX HLH Criteria (24%) (Neelapu 2017) and HLH-2004 criteria (6%). Tocilizumab was used as cytokine release syndrome (CRS) prophylaxis only by one responder. Keppra neurologic prophylaxis was used by 47.5% and 15% of responders for CAR-T and BiTE therapy, respectively. Delayed neurotoxicity with CAR-T was reported in 1-5% of patients by 57.5% of responders and 6-10% of patients by 15% of responders; most common manifestations were other movement/neuromuscular disorder (62%), nerve palsy (55%), and Parkinsonism (45%). Infectious prophylaxis was used to protect against HSV (92.5%), PJP (90%), bacterial pathogens (55%), fungal pathogens (60%), and IVIG (77.5%). However, criteria for infectious prophylaxis use varies widely incorporating IgG levels, infectious history, CD4+ count, B-cell aplasia and cytopenias (48.1 - 88.9%). Most respondents (46.3 - 86.5%) reported completing an infectious work-up including CMV, EBV, Hep B/C, and HIV ( Table 2). Conclusions: Trends of CAR-T and BiTE therapy use and patterns of concurrent prophylactic and supportive care in MM vary widely among academic centers across the globe, demonstrating a need for further understanding of toxicity pathogenesis, toxicity management and consistent guidelines. This survey also demonstrates the great unmet need for access beyond urban centers among the international myeloma community. Prospective studies and claims data analysis should be utilized to evaluate the longitudinal cost of care, quality of life, duration of response and management of infectious disease, neurological or related complications of CAR-T and bispecific TCE therapies.

8032 Background: Patients (pts) with TCE RRMM have few treatment (Tx) options and poor HRQoL. Ide-cel, the first in class CAR T cell Tx for pts with TCE RRMM, improved PFS versus standard (std) regimens in the KarMMa-3 trial. We report the PRO results comparing the Tx arms. PROs provide further understanding of Tx benefit of ide-cel from the pts’ perspective. Methods: KarMMa-3 (NCT03651128) is an open-label phase 3 RCT comparing the efficacy and safety of ide-cel with std regimens in pts with TCE RRMM, who had received 2–4 prior regimens. In addition to clinical endpoints, we evaluated the impact of ide-cel compared with std regimens on the changes in HRQoL, measured by the EORTC QLQ-C30, EORTC QLQ-MY20, and the EQ-5D-5L questionnaires. PROs were collected at baseline (screening), day of infusion and monthly from 2–24 months (mo) and thereafter every 3 mo. This interim analysis reports PROs through 20 mo. Comparisons were performed on least squares mean (LSM) changes from baseline over time between arms using constrained longitudinal data analysis (cLDA). Results: In total, 386 pts were randomized (ide-cel, 254; std regimens, 132). PRO compliance was high over time ( > 80%). At baseline, PROs were similar between arms. LSM changes from baseline to 20 mo showed significant differences ( P < 0.05), with effect sizes of 0.3–0.7, in favor of ide-cel for most domains, including global health status/QoL, cognitive functioning, fatigue, and pain (EORTC QLQ-C30); side effects of Tx (EORTC QLQ-MY20); and the EQ-5D-5L VAS. The difference in overall LSM change reached or exceeded the pre-specified between-groups minimal importance difference (MID) for improvement in most domains in favor of ide-cel (Table). Conclusions: Ide-cel showed statistically significant and clinically meaningful improvements in HRQoL, including key MM symptoms and functioning, for pts with TCE RRMM compared with std regimens. The PRO data for ide-cel expands upon the clinical outcomes observed in the KarMMa-3 trial. Clinical trial information: NCT03651128 . [Table: see text]

Summary: The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.

Abstract Background: Patients with relapsed and refractory multiple myeloma (RRMM) who have triple class exposure to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (MoABs) have a poor prognosis and high unmet medical need. Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy which may offer long-term disease control for these patients. CARTITUDE-1 is an open-label, single arm phase 1b/2 clinical trial conducted to characterize the safety and efficacy of cilta-cel in adult patients with triple-class exposed RRMM. Since CARTITUDE-1 is a single-arm study, adjusted comparisons to other currently available therapies can provide valuable information on relative efficacy and safety benefits of cilta-cel over current real-world clinical practice (RWCP). LocoMMotion is the first prospective study of RWCP efficacy and safety outcomes in triple-class exposed patients with RRMM. It was designed a priori to serve as an external control cohort for CARTITUDE-1, using aligned inclusion criteria and endpoint definitions, to enable robust, high quality indirect comparisons vs. cilta-cel. Objective: To compare patient outcomes of cilta-cel vs. RWCP, including overall response rate (ORR), complete response or better rate (≥CR rate), progression-free survival (PFS) as assessed by a review committee and overall survival (OS) in patients with triple-class exposed RRMM. Methods: Individual patient level data available from both CARTITUDE-1 (clinical cut-off February 2021) and LocoMMotion (clinical cut-off March 2021) were pooled to conduct the comparative analyses. Imbalances between both cohorts on key prognostic baseline characteristics, including refractory status, ISS stage, time to progression on prior line, number of prior lines, average duration of prior lines, age, creatinine clearance, ECOG PS and MM type were adjusted for using inverse probability weighting. Average treatment effect on the treated (ATT) weights derived from propensity scores estimated using multivariable logistic regression modeling were applied to the LocoMMotion patients to have the weighted RWCP cohort reflecting the CARTITUDE-1 patient population. Balance between the ATT weighted RWCP cohort versus the CARTITUDE-1 population was evaluated based on reduction of standardized mean differences and overlap of propensity score distributions. Weighted logistic and Cox proportional hazards regression were used to estimate the relative treatment effects for cilta-cel vs. RWCP on binary endpoints (Odds ratios (OR), transformed into Response-rate Ratios (RR) and time to event endpoints (Hazard ratios (HR)), respectively. The base case analyses included all enrolled (apheresed) patients from CARTITUDE-1, reflecting an intention to treat approach. Additional analyses were conducted including only patients who received cilta-cel infusion compared to an aligned population of LocoMMotion where patients that progressed or died within 52 days were excluded from the LocoMMotion cohort. Results: 113 patients were enrolled in CARTITUDE-1, of which 97 were infused with cilta-cel. 246 patients were enrolled in LocoMMotion receiving RWCP in Italy (24%), Germany (15%), France (14%), UK (11%), Spain (10%), USA (9%), Belgium (5%), Poland (5%), Netherlands (4%) and Russia (3%). Therapies within the RWCP cohort were diverse and &gt;90 unique treatment regimens were used. The most frequent regimens were Kd (13.8%), PCd (12.6%) and Pd (11.0%). The weighted LocoMMotion population was well balanced with the CARTITUDE-1 cohort. Adjusted comparisons (Table 1) showed statistically significant improvements for cilta-cel vs. RWCP for ORR (RR=4.43), ≥CR (RR=568.92), PFS (HR=0.15) and OS (HR=0.38), all comparisons with p&lt;0.001. All additional analyses were consistent with these findings (Table 1). Conclusions: Outcomes for patients with triple-class exposed RRMM treated with RWPC observed in LocoMMotion are poor, illustrating the high unmet medical need. Adjusted comparisons vs. CARTITUDE-1 demonstrate significantly improved ORR, ≥CR, PFS and OS for cilta-cel compared to a diverse set of RWCP. These findings highlight cilta-cel's potential as a highly effective treatment option for patients with triple-class exposed RRMM. Figure 1 Figure 1. Disclosures Mateos: Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Weisel: GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Martin: Sanofi: Research Funding; Oncopeptides: Consultancy; Janssen: Research Funding; GlaxoSmithKline: Consultancy; Amgen: Research Funding. Berdeja: Celularity, CRISPR Therapeutics: Research Funding; Abbvie, Acetylon, Amgen: Research Funding; Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy; EMD Sorono, Genentech: Research Funding; GSK, Ichnos Sciences, Incyte: Research Funding; Lilly, Novartis: Research Funding; Poseida, Sanofi, Teva: Research Funding. Jakubowiak: Karyopharm: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Gracell: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Stewart: Oncopeptides: Honoraria; Janssen: Honoraria; GSK: Honoraria; BMS: Honoraria; Amgen: Honoraria; Skyline diagnostics: Consultancy; Genomcs England: Membership on an entity's Board of Directors or advisory committees; Tempus Inc.: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; PikSci Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Sanofi Aventis: Honoraria. Jagannath: Legend Biotech: Consultancy; Bristol Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Janssen Pharmaceuticals: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. Lin: Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Legend: Consultancy; Sorrento: Consultancy; Juno: Consultancy; Takeda: Research Funding; Celgene: Consultancy, Research Funding; Gamida Cell: Consultancy; Vineti: Consultancy; Merck: Research Funding; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Perualila: Janssen: Current Employment. Cabrieto: Janssen: Current Employment. Haefliger: Janssen-Cilag AG: Ended employment in the past 24 months; Cilag GmbH International: Current Employment. Erler-Yates: Janssen: Current Employment. Hague: Janssen: Current Employment, Current equity holder in publicly-traded company. Jackson: Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Strulev: Janssen Pharmaceutica NV: Current Employment. Nesheiwat: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech: Current Employment. Moreau: Janssen: Honoraria; Celgene BMS: Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Oncopeptides: Honoraria. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding.

Abstract The primary cause of morbidity and mortality in patients with multiple myeloma (MM) is an infection. Therefore, there is great concern about susceptibility to the outcome of COVID-19–infected patients with MM. This retrospective study describes the baseline characteristics and outcome data of COVID-19 infection in 650 patients with plasma cell disorders, collected by the International Myeloma Society to understand the initial challenges faced by myeloma patients during the COVID-19 pandemic. Analyses were performed for hospitalized MM patients. Among hospitalized patients, the median age was 69 years, and nearly all patients (96%) had MM. Approximately 36% were recently diagnosed (2019-2020), and 54% of patients were receiving first-line therapy. Thirty-three percent of patients have died, with significant geographic variability, ranging from 27% to 57% of hospitalized patients. Univariate analysis identified age, International Staging System stage 3 (ISS3), high-risk disease, renal disease, suboptimal myeloma control (active or progressive disease), and 1 or more comorbidities as risk factors for higher rates of death. Neither history of transplant, including within a year of COVID-19 diagnosis, nor other anti-MM treatments were associated with outcomes. Multivariate analysis found that only age, high-risk MM, renal disease, and suboptimal MM control remained independent predictors of adverse outcome with COVID-19 infection. The management of MM in the era of COVID-19 requires careful consideration of patient- and disease-related factors to decrease the risk of acquiring COVID-19 infection, while not compromising disease control through appropriate MM treatment. This study provides initial data to develop recommendations for the management of MM patients with COVID-19 infection.