Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population‐based analysis

Pozzi, Samantha; Marcheselli, Luigi; Bari, Alessia; Liardo, Eliana Valentina; Marcheselli, Raffaella; Luminari, Stefano; Quaresima, Micol; Crimi, Claudia; Ferri, Paola; Fédérico, Massimo; Sacchi, Stefano

doi:10.1111/bjh.12465

Cited by 84 publications

(76 citation statements)

References 14 publications

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“…Importantly, we followed a strategy of applying 200mg/m2 melphalan before ASCT in myeloma patients below 70 years, and we reduced melphalan to 140mg/m2 for mg/m2 in elderly myeloma patients was reported to be up to 19% (17), while that for 100 mg/m2 of melphalan was 0% (19) and 2% for 140 mg/m2 melphalan (20). Our single-center results with a TRM of 0% in 71 myeloma patients aged 66-69 years treated with 200mg/m2 melphalan challenge the need for dose reductions in myeloma patients in this age cohort considered to be fit for high-dose consolidation.…”

Section: Discussionmentioning

confidence: 99%

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Autologous stem cell transplantation in elderly patients with multiple myeloma: evaluation of its safety and efficacy

Stettler

Novak

Baerlocher

et al. 2016

Leukemia & Lymphoma

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Administering high-dose chemotherapy (HDCT) with melphalan to elderly myeloma patients represents a challenge with respect to achieving therapeutic efficacy whilst avoiding significant toxicity. We analyzed safety and efficacy of HDCT in 61 elderly myeloma patients older than 65 years, including 12 patients ≥70 years, and compared them to 237 MM patients below 65 years treated in the same period. MM patients older than 70 years had a longer duration of hospitalization (26 vs. 20 days;P=.0001) and a longer time until platelet recovery >20 G/L (19 vs. 15 days; P=.0398). However, we observed no differences in the time until neutrophil recovery, infection rate, and treatment related mortality until 100 days after ASCT.Furthermore, higher age was not associated with inferior progression-free and overall survival at 1 and 2 years after ASCT. Our data suggest that HDCT with ASCT is feasible, safe and effective in MM patients older than 65 years. Stettler et alAutologous transplant in elderly myeloma patients.

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Section: Discussionmentioning

confidence: 99%

“…However, the significant improvement in overall survival has mainly been observed in younger MM patients [11][12][13][14][15][16][17], whereas advances for elderly MM patients have been less significant [11,14,16,18].…”

Section: Introductionmentioning

confidence: 99%

Autologous stem cell transplantation in elderly patients with multiple myeloma: evaluation of its safety and efficacy

Stettler

Novak

Baerlocher

et al. 2016

Leukemia & Lymphoma

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“…The median number of study treatment cycles was 6 (range [1][2][3][4][5][6][7][8][9][10][11][12][13] and 49 patients (70%) received 90% of the relative intended dose of elotuzumab. Of the 1,113 elotuzumab infusions given, 87% (968) were given at the maximum 5 mL/min rate; of the remaining 13% (145), 144…”

Section: R E S U L T S 31 | Patients and Dosingmentioning

confidence: 99%

“…1 In recent years, several new therapeutic agents have been introduced. [2][3][4][5] Current treatment guidelines recommend autologous stem cell transplantation (when eligible), chemotherapy (melphalan, cyclophosphamide, or pegylated liposomal doxorubicin), proteasome inhibitor (PI)-based regimens (bortezomib, carfilzomib, or ixazomib), and immunomodulatory drug (IMiD)-based regimens (thalidomide, lenalidomide, or pomalidomide), often coupled with a corticosteroid (eg, dexamethasone). Combined treatments (usually three agents; triplets) have been notably effective in improving patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

A phase 2 safety study of accelerated elotuzumab infusion, over less than 1 h, in combination with lenalidomide and dexamethasone, in patients with multiple myeloma

Berenson

Manges²,

Badarinath

et al. 2017

American J Hematol

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Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/ refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, 3-h infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM. The primary endpoint was cumulative incidence of Grade 3/4IRs by completion of treatment Cycle 2. Dosing comprised elotuzumab 10 mg/kg intravenously (weekly, Cycles 1-2; biweekly, Cycles 31), lenalidomide 25 mg (daily, Days 1-21), and dexamethasone (28 mg orally and 8 mg intravenously, weekly, Cycles 1-2; 40 mg orally, weekly, Cycles 31), in 28-day cycles. Premedication with diphenhydramine, acetaminophen, and ranitidine (or their equivalents) was given as in previous studies. If no IRs occurred, infusion rate was increased in Cycle 1 from 0.5 to 2 mL/min during dose 1 ( 2 h 50 min duration) to 5 mL/min for the entire infusion by dose 3 and also during all subsequent infusions ( 1-h duration). Median number of treatment cycles was six. No Grade 3/4 IRs occurred; only one Grade 1 and one Grade 2 IR occurred, both during the first infusion. These data support the safety of a faster infusion of elotuzumab administered over 1 h by the third dose, providing a more convenient alternative dosing option for patients.

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“…15,[21][22][23] In aggregate, it appears that while the incidence of multiple myeloma is rising, mortality rates are dropping. Because our study used aggregate population estimates, the issue of competing risks between non-renal death and ESRD could not be addressed.…”

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confidence: 99%

ESRD due to Multiple Myeloma in the United States, 2001–2010

Reule

Sexton

Solid

et al. 2015

JASN

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Although management of multiple myeloma has changed substantially in the last decade, it is unknown whether the burden of ESRD due to multiple myeloma has changed, or whether survival of patients with multiple myeloma on RRT has improved. Regarding ESRD due to multiple myeloma necessitating RRT in the United States, we evaluated temporal trends between 2001 and 2010 for demography-adjusted incidence ratios, relative to rates in [2001][2002], and mortality hazards from RRT initiation, relative to hazards in [2001][2002]. In this retrospective cohort study, we used the US Renal Data System database (n=1,069,343), 2001-2010, to identify patients with ESRD due to multiple myeloma treated with RRT (n=12,703). Demography-adjusted incidence ratios of ESRD from multiple myeloma decreased between 2001-2002 and 2009-2010 in the overall population (demography-adjusted incidence ratio 0.82; 95% confidence interval, 0.79 to 0.86) and in most demographic subgroups examined. Mortality rates were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, respectively, compared with 32.3, 20.6, and 21.3 in matched controls without multiple myeloma. Unadjusted mortality hazards ratios declined monotonically after 2004 to a value of 0.72; 95% confidence interval, 0.67 to 0.77 in 2009-2010, and declines between 2001-2002 and 2008-2009 were observed (P,0.05) in most demographic subgroups examined. Findings were similar when adjustment was made for demographic characteristics, comorbidity markers, and laboratory test values. These data suggest the incidence of RRT from multiple myeloma in the United States has decreased in the last decade, and clinically meaningful increases in survival have occurred for these patients.

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Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population‐based analysis

Cited by 84 publications

References 14 publications

Autologous stem cell transplantation in elderly patients with multiple myeloma: evaluation of its safety and efficacy

Autologous stem cell transplantation in elderly patients with multiple myeloma: evaluation of its safety and efficacy

A phase 2 safety study of accelerated elotuzumab infusion, over less than 1 h, in combination with lenalidomide and dexamethasone, in patients with multiple myeloma

ESRD due to Multiple Myeloma in the United States, 2001–2010

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