Early relapse after autologous transplant for myeloma is associated with poor survival regardless of cytogenetic risk

Corre, Jill; Montes, Lydia; Martin, E.; Perrot, Aurore; Caillot, Denis; Leleu, Xavier; Belhadj, Karim; Facon, Thierry; Hulin, Cyrille; Mohty, Mohamad; Fontan, Jean; Macro, Margaret; Bréchignac, Sabine; Jaccard, Arnaud; Stoppa, Anne‐Marie; Orsini‐Piocelle, Frédérique; Adiko, Didier; Voillat, Laurent; Keddar, Faiza; Barry, Marly; Demarquette, Hélène; Certain, Marie-Noëlle; Plantier, Isabelle; Roussel, Murielle; Hébraud, Benjamin; Filleron, Thomas; Attal, Michel; Avet‐Loiseau, Hervé

doi:10.3324/haematol.2019.236588

Cited by 53 publications

(51 citation statements)

References 15 publications

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“…HRD with gain (11) HRD no gain (11) t (4;14) t (6;14) t (11;14) t We demonstrate, to our knowledge for the first time, in a randomized controlled trial that acquisition of gain(1q) at relapse is independently and strongly associated with inferior OS [36]. Although findings are also indicative for del(17p), del(1p/CDKN2C) and gain(8q/MYC), our power to robustly assert clinical relevance of acquired lesions at relapse is inevitably limited by the lower frequency of these CNAs [37].…”

Section: Discussionmentioning

confidence: 66%

Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial

et al. 2020

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Structural chromosomal changes including copy number aberrations (CNAs) are a major feature of multiple myeloma (MM), however their evolution in context of modern biological therapy is not well characterized. To investigate acquisition of CNAs and their prognostic relevance in context of first-line therapy, we profiled tumor diagnosis–relapse pairs from 178 NCRI Myeloma XI (ISRCTN49407852) trial patients using digital multiplex ligation-dependent probe amplification. CNA profiles acquired at relapse differed substantially between MM subtypes: hyperdiploid (HRD) tumors evolved predominantly in branching pattern vs. linear pattern in t(4;14) vs. stable pattern in t(11;14). CNA acquisition also differed between subtypes based on CCND expression, with a marked enrichment of acquired del(17p) in CCND2 over CCND1 tumors. Acquired CNAs were not influenced by high-dose melphalan or lenalidomide maintenance randomization. A branching evolution pattern was significantly associated with inferior overall survival (OS; hazard ratio (HR) 2.61, P = 0.0048). As an individual lesion, acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse (HR = 2.00; P = 0.021). There is an increasing need for rational therapy sequencing in MM. Our data supports the value of repeat molecular profiling to characterize disease evolution and inform management of MM relapse.

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Section: Discussionmentioning

confidence: 66%

Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial

et al. 2020

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“…MM usually affects the elderly population, a more vulnerable group of patients due to immunosenescence together with other comorbidities. In addition, younger MM patients are usually treated with high-dose chemotherapy followed by autologous stem cell transplant, 13 with high infection susceptibility during the 3-month period following transplant. 14 For all of these reasons, MM could theoretically represent a high risk factor for poor outcomes with COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set

Chari

Samur

Martínez‐López

et al. 2020

Blood

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The primary cause of morbidity and mortality in patients with multiple myeloma(MM) is an infection. Therefore there is great concern about the 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 COVID-19 pandemic. Analysis were performed for hospitalized MM patients. Among hospitalized patinets, 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, ISS3, high-risk disease, renal disease, suboptimal myeloma control(active or progressive disease), and one 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.

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“…Although these data are undoubtedly helpful, they are not necessarily the be all and end all. One study 3 found that roughly two-thirds of people who relapsed within 18 months of therapy had not been classed as having high-risk disease from their original genetic screening.…”

Section: A Diversifying Diseasementioning

confidence: 99%

Will the reclassification of multiple myeloma change how people are treated?

Plackett¹

2020

Nature

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Early relapse after autologous transplant for myeloma is associated with poor survival regardless of cytogenetic risk

Cited by 53 publications

References 15 publications

Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial

Copy number evolution and its relationship with patient outcome—an analysis of 178 matched presentation-relapse tumor pairs from the Myeloma XI trial

Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set

Will the reclassification of multiple myeloma change how people are treated?

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