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Objectives: Gain or amplification of 1q21 (1q21+, ≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma (MM), has a negative impact on prognosis due to its potential involvement in resistance to MM therapy and disease progression. In this subgroup analysis of IKEMA, we evaluated efficacy of isatuximab-carfilzomib-dexamethasone (Isa-Kd) in patients (pts) with 1q21+ status (with or without high-risk chromosomal abnormalities [HRCA]) and related subgroups – isolated 1q21+ (≥ 3 copies without HRCA), gain(1q21), amp(1q21) – at long-term follow-up (44.2 months). Methods: Pts with 1–3 prior lines of therapy were randomized to Isa-Kd (n = 179) or Kd (n = 123). Assessment was prespecified (at 30% cutoff by FISH) for 1q21+ status as ≥3 copies, gain(1q21) as 3 copies, and amp(1q21) as ≥4 copies. Results: In the Isa-Kd and Kd arms, 41.9% and 42.3% of pts had 1q21+ status, 26.3% and 25.2% isolated 1q21+, 24.0% and 30.1% gain(1q21), 17.9% and 12.2% amp(1q21) respectively. Greater progression-free survival (PFS) benefit was achieved with Isa-Kd vs Kd in pts with 1q21+ status (hazard ratio [HR] 0.58, 95% CI 0.37–0.92) and in pts with isolated 1q21+, gain(1q21), or amp(1q21). Responses deepened by adding Isa to Kd, with increased rates of very good partial response or better (≥VGPR), complete response or better (≥CR), minimal residual disease negativity (MRD-), and MRD- ≥CR. Discussion: In the prespecified, long-term analysis of the Phase 3 IKEMA trial in relapsed MM pts, treatment with Isa-Kd showed continued, significant improvement in PFS compared to Kd (HR 0.58; 95.4% CI 0.42–0.79). There was a meaningful increase in the depth of response (≥CR 44.1% vs 28.5%; MRD- 33.5% vs 15.4%, MRD- ≥CR 26.3% vs 12.2%), and a manageable safety profile. The present study demonstrated that Isa-Kd led to deeper responses, with higher ≥VGPR rates, MRD-, and MRD- ≥CR rates in 1q21+ patients (with or without HRCA), isolated 1q21+, gain(1q21), or amp(1q21) compared to Kd. These long-term findings support Isa-Kd as an effective treatment option for patients with relapsed MM, including 1q21+ abnormalities and a higher risk of progression. Conclusions: 1q21 abnormalities may affect PFS in MM pts. Our results at long-term follow-up of pts with 1q21+ status (with or without HRCA) in the IKEMA study continue to show greater PFS benefit and deeper responses with Isa-Kd than Kd, consistent with the overall population and earlier 1q21+ subgroup interim analyses. Thus, they support Isa-Kd as an effective treatment option also for difficult-to-treat, 1q21+ pts with relapsed MM.

Background: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs., Results: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger ( p = 0.05) and more frequently had a prior AutoHCT ( p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS., Conclusions: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success., Methods: A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions., Results: This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers., Conclusion: We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil., Competing Interests: Conflicts of interest AAP: Honoraria from lectures: BMS, Janssen, Gilead-Kite, Astellas, Jazz Pharmaceuticals Participation in Advisory Board meetings: BMS, Jazz Pharmaceuticals Consultant: Astellas AM: Honoraria from lectures: BMS, Janssen, Sanofi, Amgen, Takeda Participation in Advisory Board meetings: BMS, Janssen, Sanofi, Takeda, Pfizer Consultant: BMS, Pfizer, Astra Zeneca, Novartis, Janssen EC: Research funding: Janssen JSF: Honoraria from lectures and Advisory Boards: Janssen, Novartis, Kite/Gilead, BMS, Abbvie, Amgen. RM: Honoraria for lectures and boards: Janssen, Sanofi, Takeda, Amgen, BMS PRO: Honoraria from lectures: BMS, Janssen, Sanofi, GSK, Amgen, Regeneron, Takeda Participation in Advisory Board meetings: BMS, Janssen, Sanofi, Kite Pharma, Abbvie, Oncopeptides, Takeda, Pfizer, GSK Consultant: BMS, Pfizer VH: Honoraria from lectures: Amgen, BMS, GSK, Janssen, Sanofi, Takeda Participation in Advisory Board meetings: BMS, Janssen, Pfizer, Sanofi, (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)