Pomalidomide, bortezomib, and dexamethasone at first relapse in lenalidomide‐pretreated myeloma: A subanalysis of OPTIMISMM by clinical characteristics

Richardson, Paul G.; Schjesvold, Fredrik; Weisel, Katja; Moreau, Philippe; Anderson, Larry D.; White, Darrell; Rodríguez‐Otero, Paula; Sonneveld, Pieter; Engelhardt, Monika; Jenner, Matthew; Corso, Alessandro; Dürig, Jan; Pavic, Michel; Salomo, Morten; Beksaç, Meral; Oriol, Albert; Lindsay, Jindriska; Liberati, Anna Marina; Galli, Mónica; Robak, Paweł; Larocca, Alessandra; Yağcı, Münci; Vural, Fılız; Kanate, Abraham S.; Jiang, Ruixuan; Grote, Lara; Peluso, Teresa; Dimopoulos, Meletios A.

doi:10.1111/ejh.13706

Cited by 10 publications

(13 citation statements)

References 38 publications

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“…However, the publishing of subgroup safety analyses of clinical trials in elderly populations should be encouraged, given the few currently available [77,[80][81][82][83][84]. Frail patients should still receive the best appropriate treatment with dose reductions to be evaluated over time in each patient to avoid under-treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Most RRMM clinical trials define high-risk cytogenetics according to IMWG criteria, with ≥1 of del(17p), t(4;14) and/or t(14;16). 1q21+ is only considered as a high-risk CA in the ICARIA-MM, IKEMA and BOSTON trials [25,[34][35][36][37][38][39][40][41][42][43].…”

Section: Risk Stratification Of High-risk Cytogenetics Definitions Va...mentioning

confidence: 99%

“…Subgroup analysis of phase 3 RRMM trials show that, in most cases, newer agents have provided clinical benefit to patients regardless of cytogenetic risk (Table 2; not intended for direct comparison). Of the listed trials, ICARIA-MM, IKEMA, APOLLO, CANDOR, CASTOR, OPTIMISMM and ELOQUENT-3 enrolled lenalidomide-refractory or IMiD-refractory patients [25,[34][35][36][38][39][40]. Anti-BCMA therapies are currently under development, and subgroup analyses of patients with high-risk cytogenetics of phase 2 trials have been published, namely from the KarMMA trial (investigating idecabtagene vicleucel), DREAMM-2 trial (belantamab mafodotin), and CARTITUDE-1 (ciltacabtagene vicleucel) [43,[46][47][48][49].…”

Section: Impact Of High-risk Cytogenetics In Clinical Trialsmentioning

confidence: 99%

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Difficult‐to‐treat patients with relapsed/refractory multiple myeloma: A review of clinical trial results

Raab

Zamagni²,

Manier³

et al. 2023

eJHaem

Self Cite

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Overall outcomes for multiple myeloma have improved due to the availability of new therapies, but patients with relapsed/refractory multiple myeloma harbouring certain factors continue to pose a therapeutic challenge. These challenging features include high‐risk cytogenetics, renal impairment, patient characteristics such as age and frailty, and extramedullary disease. Prior refractory status and number of prior lines add further complexity to the treatment of these patients. While newer regimens are available and have suggested efficacy in these patient populations through subgroup analyses, differences in trial definitions and cut‐offs make meaningful comparisons difficult. This review aims to examine the available clinical trial data for patients with high‐risk cytogenetics, renal impairment, age and frailty and extramedullary disease.

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Section: Discussionmentioning

confidence: 99%

Section: Risk Stratification Of High-risk Cytogenetics Definitions Va...mentioning

confidence: 99%

Section: Impact Of High-risk Cytogenetics In Clinical Trialsmentioning

confidence: 99%

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Difficult‐to‐treat patients with relapsed/refractory multiple myeloma: A review of clinical trial results

Raab

Zamagni²,

Manier³

et al. 2023

eJHaem

Self Cite

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show abstract

“…There are limited subgroup analyses in RRMM addressing patients with RI; however, the definition of RI differed between trials making interpretations and comparisons of the results difficult. ORRs using triplet combinations range between 56.4% (ICARIA) to up to 91.4% and 93.1% (OPTIMISMM, IKEMA) [ 82 , 83 , 84 ]. Even an improvement in OS could be demonstrated with Isa-Pd [ 82 ] (ICARIA) but also the double Kd [ 85 ].…”

Section: Patient-related Factors With Impact On Decision-makingmentioning

confidence: 99%

Stratification for RRMM and Risk-Adapted Therapy: Sequencing of Therapies in RRMM

Jeryczynski

Bolomsky

Agis

et al. 2021

Cancers

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The treatment landscape for relapsed multiple myeloma (RRMM) has experienced an unprecedented wave of innovation. Implementation of numerous new substances and drug classes with different modes of action is made possible in routine clinical practice. Next generation proteasome inhibitors, monoclonal antibodies, as well as first in class agents such as selinexor and venetoclax have widened the therapeutic spectrum. This has led to an increase in progression-free and overall survival. Consequently, new challenges for treating physicians in choosing the right treatment at the right stage of the disease have been generated. Several trials support the use of novel agents in the frontline treatment of newly diagnosed multiple myeloma. The use of lenalidomide or bortezomib as a backbone in the first-line setting, requires strategies for treatment once these patients relapse and are refractory to these drugs. Despite the variety of options, selecting the optimal treatment strategy is difficult, since multiple factors have to be considered: patient-specific factors such as age and co-morbidities, as well as myeloma/tumor specific factors such as cytogenetics and relapse kinetics. This review intends to summarize the existing data and guidelines regarding the optimal sequencing of treatments of RRMM using already approved agents as well as agents under investigation.

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“…1 However, its therapeutic effect is limited, and the high recurrence rate and poor prognosis of MM patients remain one of the most challenging problems. 4,5 Therefore, it is urgently need to explain the pathogenesis of MM in order to develop new effective therapeutic strategies for MM.…”

Section: Introductionmentioning

confidence: 99%

LncRNA FEZF1‐AS1 accelerates multiple myeloma progression by regulating IGF2BP1/BZW2 signaling

Long

Wen

et al. 2023

Hematological Oncology

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Multiple myeloma (MM) is the second largest hematological tumor with clonal proliferation of malignant plasma cells. Growing reports have revealed that the dysregulation of long non‐coding RNA (lncRNA) is involved in the MM progression. Nevertheless, lncRNA FEZF1 antisense RNA 1 (FEZF1‐AS1) remain not deeply explored. The RNA transcripts and protein level of MM‐associated molecule were measured by quantitative real‐time polymerase chain reaction or western blot assays, respectively. The clinical correlation was analyzed by Pearson analysis. Molecular interactions among lncRNA FEZF1‐AS1, basic leucine zipper and W2 domain 2 (BZW2) and insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) were verified by RNA immunoprecipitation and RNA pull‐down assays. The survival of MM cells was detected by cell counting kit‐8 and flow cytometry assays. Xenograft tumor in vivo was performed to assess tumor growth. The RNA transcripts of lncRNA FEZF1‐AS1, BZW2 and IGF2BP1 were upregulated in MM samples compared to those in healthy donors. Knockdown of lncRNA FEZF1‐AS1 could inhibit the proliferation and induce cell apoptosis in vitro and in vivo. Besides, lncRNA FEZF1‐AS1 could maintain the stability of BZW2 mRNA by interacting IGF2BP1. Moreover, BZW2 silence also downregulated the proliferation but enhanced apoptosis of MM cells, while BZW2 overexpression had an opposite role, which dramatically reversed the regulatory roles of lncRNA FEZF1‐AS1. Altogether, lncRNA FEZF1‐AS1 facilitated MM development by regulating IGF2BP1/BZW2 signaling, suggesting that lncRNA FEZF1‐AS1 might be a candidate for MM treatment.

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Pomalidomide, bortezomib, and dexamethasone at first relapse in lenalidomide‐pretreated myeloma: A subanalysis of OPTIMISMM by clinical characteristics

Cited by 10 publications

References 38 publications

Difficult‐to‐treat patients with relapsed/refractory multiple myeloma: A review of clinical trial results

Difficult‐to‐treat patients with relapsed/refractory multiple myeloma: A review of clinical trial results

Stratification for RRMM and Risk-Adapted Therapy: Sequencing of Therapies in RRMM

LncRNA FEZF1‐AS1 accelerates multiple myeloma progression by regulating IGF2BP1/BZW2 signaling

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