Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation

Shah, Gunjan L.; Landau, Heather; Londono, Dory; Devlin, Sean M.; Kosuri, Satyajit; Lesokhin, Alexander M.; Lendvai, Nikoletta; Hassoun, Hani; Chung, David J.; Koehne, Guenther; Jhanwar, Suresh C.; Landgren, Ola; Levine, Ross L.; Giralt, Sergío

doi:10.1080/10428194.2016.1260126

Cited by 60 publications

(66 citation statements)

References 32 publications

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“…To further evaluate the potential benefit of ASCT, we measured PFS and OS from the date of transplantation. In our study, ASCT after bortezomib induction could change the poor prognosis since the date of transplantation in patients with MM with 1q21 gain, although the difference was not the same in all cohorts .…”

Section: Discussionmentioning

confidence: 60%

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China

Chen

et al. 2019

The Oncologist

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Section: Discussionmentioning

confidence: 60%

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China

Chen

et al. 2019

The Oncologist

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“…Of the 31 evaluable patients, 12 patients had the following cytogenetic abnormalities: 5 (16%) 1q amplification, 5 (16%) 17p deletion, and 2 (6%) t(4,14) and 1q amplification. (Although gains in chromosome 1q have been identified as a poor prognostic marker by several studies, 27 - 30 the IMWG classification of cytogentically high-risk disease does not currently encompass this abnormality.) Six patients had normal cytogenetics, and the cytogenetic profile is unknown or was not done for 13 patients.…”

Section: Resultsmentioning

confidence: 99%

Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma

et al. 2018

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In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose limiting. Per 3+3 phase I design, an additional 3 patients were enrolled to DL1, with no further dose limiting toxicity (DLT). At dose level 2 (DL2, 4 mg Ixa), 1/3 patients had dose-limiting febrile neutropenia, neutropenia, and thrombocytopenia (grade 4 each). DL2 was expanded to enroll 3 additional patients with no further DLT, establishing the recommended phase II dose (RP2D). In phase II, 19 additional patients were treated at RP2D. With a median follow-up of 11.9 months, 48% achieved ≥partial response (PR), with 5 patients (20%) achieving very good partial response (VGPR) and 76% experiencing ≥stable disease. The most common adverse events (≥grade 2) were anemia, neutropenia, thrombocytopenia, and infections. Peripheral neuropathy was infrequent. In summary, Ixa/Pom/Dex is a well-tolerated and effective oral combination therapy for patients with relapsed/refractory MM.

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“…There is substantial genetic complexity in MM, and multiple primary and secondary cytogenetic abnormalities can potentially impact outcomes 31 , 49 . Not all of the abnormalities now recognized as conferring poor prognosis are routinely collected or reported in clinical trials or observational studies, including deletion 17 [del(17)], the translocations t(4;14), and t(14;16) 19 , 20 , 1q amplification 50 , and 1p deletion 51 . The proportion of patients with cytogenetics reported is often low in clinical trials (e.g., 47% of patients in FIRST; 9 53% in ASPIRE 52 ), leading to a high level of missing information, although this proportion was higher in the TOURMALINE-MM1 (76%) 20 , CASTOR (71%) 16 , and POLLUX (77%) 15 trials.…”

Section: The Impact Of Disease and Patient Heterogeneity On Clinical mentioning

confidence: 99%

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Richardson

Miguel

Moreau³

et al. 2018

Blood Cancer Journal

197

174

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Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/refractory MM on novel agent−based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients’ treatment approaches.

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Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation

Cited by 60 publications

References 32 publications

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China

Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

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