Carfilzomib, lenalidomide, and low-dose dexamethasone in elderly patients with newly diagnosed multiple myeloma

Dytfeld, Dominik; Jasielec, Jagoda; Griffith, Kent A.; Lebovic, Daniel; Jagannath, Sundar; Al-Zoubi, Ammar; Anderson, Tara; Detweiler-Short, Kristen; Stockerl-Goldstein, Keith; Ahmed, Asra; Jobkar, Terri L.; Durecki, Diane; McDonnell, Kathryn; Mietzel, Melissa A.; Couriel, Daniel R.; Kaminski, Mark; Vij, Ravi; Jakubowiak, Andrzej

doi:10.3324/haematol.2014.110395

Cited by 43 publications

(36 citation statements)

References 15 publications

(12 reference statements)

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“…All patients remained free of progression and alive at the median follow up of 1 year (see Table 1). 33 These results support a phase III study of CRd versus Rd in all age groups.…”

Section: Regimens Based On Proteasome Inhibitors and Immunoregulatorysupporting

confidence: 80%

How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients?

Mateos¹

2015

Oncology &Amp; Hematology Review (US)

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Touch MEdical MEdia 43Multiple myeloma (MM) is an incurable plasma cell disease that comprises 1 % of all cancers and 10 % of hematologic malignancies. It primarily affects older individuals-the median age at the moment of diagnosis is 70 years-and two-thirds of multiple myeloma patients are over 65 years of age when they are first diagnosed. The outcome of MM patients has significantly improved in the last decade.1,2 However, the main benefit has accrued to young patients, due to the introduction of high-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) that are upfront and novel agents as rescue therapy, while only a marginal change has been observed in patients older than 65 years. However, the availability of new frontline treatment regimens based on the novel agents thalidomide, bortezomib, and lenalidomide has extended the options for transplant-ineligible MM patients.In parallel with the advances in treatment options, goals of therapy have also evolved for non-transplant candidate patients. While prolongation of disease-free and overall survival remain the ultimate goal, to achieve prolonged treatment-free intervals and good quality of life also become important aims. Moreover, in the era of melphalan plus prednisone (MP), the goal was to achieve partial response (PR); by contrast, nowadays with the new agents, complete response (CR) has become the new goal also in elderly patients. Thus, in a retrospective analysis on pooled data of 1,175 patients with newly diagnosed MM, treated with MP and novel agents, the achievement of CR was associated with improved progressionfree survival (PFS) and overall survival (OS): the 3-year PFS was 67 % in patients who achieved CR versus 27 % in those in very good PR (VGPR) or PR, whereas the 3-year OS rates were 91 % in patients who obtained CR and 67 % to 70 % in those in VGPR or PR. 3 Moreover, upon using more sensitive parameters, such as free-light chain and multiparameter flow cytometry, to define the depth of response, a Spanish group has shown, in a prospective analysis conducted in elderly patients receiving novel agents, that to achieve immunophenotypic response translated into superior PFS and OS compared with the presence of minimal residual disease after induction. Therefore, to monitor treatment efficacy with highly sensitive techniques should also be an objective in the treatment of elderly patients, since this could help clinicians to define the optimal level of response and to individualize treatment intensity and duration, with an appropriate balance with toxicity.This review will provide a summary of data supporting the current management of elderly patients with newly diagnosed MM. The second generation of novel agents will be also evaluated. The potential role of AbstractMultiple myeloma is the second most frequent hematologic disease, which usually affects patients over 65 years of age. Treatment goals for these non-transplant-eligible patients should be to prolong survival by achieving the best response, while ensuring qual...

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“…All patients remained free of progression and alive at the median follow up of 1 year (see Table 1). 33 These results support a phase III study of CRd versus Rd in all age groups.…”

Section: Regimens Based On Proteasome Inhibitors and Immunoregulatorysupporting

confidence: 80%

How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients?

Mateos¹

2015

Oncology &Amp; Hematology Review (US)

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“…Carfilzomib plus Rd resulted in a 100% overall response rate (ORR) with 65% stringent CR, and bortezomib plus Rd also in a 100% ORR with a 52% CR rate. 10,11 In line with this, if we consider the results reported in the MM-015 trial in which the addition of lenalidomide to MP gave a significantly better PFS but not a longer OS, and in which there was a high frequency of adverse effects, especially in patients older than 75 years, 12 we may conclude that melphalan is not the best partner for combining with immunomodulatory drugs, but is nevertheless an excellent drug in combination with bortezomib, as our analysis suggests. Furthermore, the combination of second-generation proteasome inhibitors with MP is yielding promising results.…”

Section: Discussionmentioning

confidence: 99%

GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?

Mateos¹,

Oriol

Martínez‐López

et al. 2014

Blood

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“…14 Although the achievement of MRD negativity predicted for a significant prolongation in time-to progression (TTP) [15][16][17] and OS 18 in the PETHEMA/GEM2005MAS65 study, no statistically significant differences in survival were noted between MRD-negative and positive patients in the nonintensive pathway of the MRC Myeloma IX clinical trial 19 ; therefore, although recent studies indicate that high MRD-negative rates can be achieved by a significant number of transplant-ineligible patients treated with optimized therapeutic combinations, 20,21 the clinical significance of MRD monitoring in patients with elderly MM remains an (important) open question.…”

Section: Introductionmentioning

confidence: 99%

Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients

Paiva

Cedena

Puig

et al. 2016

Blood

129

116

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Key Points• MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespective of age or cytogenetic risk.• Second-generation MFC immune profiling concomitant to MRD monitoring also helped to identify patients with different outcomes.The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first-to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10 25; n 5 54, 34%), MRD positive (between <10 24and ‡10 25 ; n 5 20, 12%), and MRD positive ( ‡10 24 ; n 5 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P 5 .007) and overall survival (OS) (HR, 3.1; P 5 .04), with significant benefit for MRDnegative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10 24 and ‡10 25 vs ‡10 24 (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P 5 .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P 5 .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249. (Blood. 2016;127(25):3165-3174)

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Carfilzomib, lenalidomide, and low-dose dexamethasone in elderly patients with newly diagnosed multiple myeloma

Cited by 43 publications

References 15 publications

How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients?

How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients?

GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators?

Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients

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