Pomalidomide plus low-dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure

Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM-014 trial, we examined the safety and efficacy of pomalidomide plus low-dose dexamethasone immediately after lenalidomide-based treatment failure in patients with RRMM and two prior lines of therapy. Pomalidomide 4 mg was given on days 1 to 21 of 28-day cycles. Dexamethasone 40 mg (20 mg for patients aged >75 years) was given on days 1, 8, 15 and 22 of 28-day cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. The intention-to-treat population comprised 56 patients; all received prior lenalidomide (87·5% lenalidomide refractory) and 39 (69·6%) received prior bortezomib. ORR was 32·1% (28·2% in the prior-bortezomib subgroup). Median PFS was 12·2 months (7·9 months in the prior-bortezomib subgroup). Median OS was 41·7 months (38·6 months in the prior-bortezomib subgroup). The most common grade 3/4 treatment-emergent adverse events were anaemia (25·0%), pneumonia (14·3%) and fatigue (14·3%). These findings support earlier sequencing of pomalidomide-based therapy in lenalidomide-pretreated patients with RRMM, including those who have become refractory to lenalidomide. Trial registration: www.ClinicalTrials.gov identifier NCT01946477.     

Lenalidomide,bendamustine and prednisolone exhibits a favourable safety and efficacy profile in relapsed or refractory multiple myeloma: final results of a phase 1 clinical trial OSHO – #077

This phase 1 dose finding study tested a combination of lenalidomide, bendamustine and prednisolone (RBP) in 21 patients in five cohorts with advanced multiple relasped/refractory myeloma (MM) to determine the maximum tolerable dose (MTD) of the combination. The first cohort received a starting dose of lenalidomide 10 mg/d, days 1–21, bendamustine 60 mg/m²/d, days 1–2, and prednisolone 100 mg/d, days 1–4. Dose escalation was done in cohorts of three to six patients with lenalidomide dose increasing to 15, 20 and 25 mg, and after reaching 25 mg/d, bendamustine was increased to 75 mg/m². A total of 21 patients were enrolled and all completed at least two cycles. Two patients developed dose‐limiting haemotoxicity: one patient on lenalidomide 25 mg/d and bendamustine 60 mg/m² and another patient at the highest dose level (lenalidomide 25 mg/d and bendamustine 75 mg/m²). The MTD was not reached. Sixteen patients (76%) responded after at least two cycles of RBP with one stringent complete response (CR), one near CR, five very good partial response and nine partial response. After a median observation time of 16 months, progression‐free survival at 18 months was 48% and overall survival was 64%. In conclusion, RBP with lenalidomide 25 mg/d, days 1–21 and bendamustine 75 mg/m² days 1–2 is well tolerated in patients with relapsed/refractory MM.     

Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma

Lenalidomide gained Food and Drug Administration (FDA) approval for treatment of patients with relapsed or refractory multiple myeloma (MM) in combination with dexamethasone in June 2006. In April 2005, the FDA and patient advocacy groups requested an expanded access programme to both provide lenalidomide to patients likely to benefit and obtain additional safety information. Relapsed/refractory MM patients received lenalidomide 25 mg/d (days 1–21) and dexamethasone 40 mg/d (days 1–4, 9–12, and 17–20 of cycles 1–4; days 1–4 only from cycle 5 onwards), in 4-week cycles until disease progression, study drug discontinuation, or lenalidomide approval. Of the 1438 patients enrolled, ∼60% were male, median age was 64 years, and 61·7% had Durie-Salmon stage III disease. Median time on study was 15·4 weeks (range: 0·1–49·1) and median dose was 25 mg. The most common adverse events (AEs) were haematological (49%), gastrointestinal (59%), and fatigue (55%). The most common grade ≥3 AEs were haematological (45%), fatigue (10%), and pneumonia (7%). The most common serious AEs were pneumonia (8%), pyrexia (4%), and deep-vein thrombosis (3%). Primary cause of death was disease progression (10%). Safety data confirmed known AEs of lenalidomide plus dexamethasone therapy in patients with relapsed/refractory MM.     

Bendamustine,thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trial

There is a significant unmet need in effective therapy for relapsed myeloma patients once they become refractory to bortezomib and lenalidomide. While data from the front line setting suggest bendamustine is superior to melphalan, there is no information defining optimal bendamustine dose in multiply‐treated patients. We report a multi‐centre randomized two‐stage phase 2 trial simultaneously assessing deliverability and activity of two doses of bendamustine (60 mg/m² vs. 100 mg/m²) days 1 and 8, thalidomide (100 mg) days 1–21 and low dose dexamethasone (20 mg) days 1, 8, 15 and 22 of a 28‐d cycle. Ninety‐four relapsing patients were treated on trial, with a median three prior treatment lines. A pre‐planned interim deliverability and activity assessment led to closure of the 100 mg/m² arm due to excess cytopenias, and led to amendment of entry criteria for cytopenias. Non‐haematological toxicities including thromboembolism and neurotoxicity were infrequent. In the 60 mg/m² arm, treatment was deliverable in 61·1% subjects and the partial response rate was 46·3% in the study eligible population, with 7·5 months progression‐free survival. This study demonstrates bendamustine at 60 mg/m² twice per month with thalidomide and dexamethasone is deliverable for repeated cycles in heavily pre‐treated myeloma patients and has substantial clinical activity.     

Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma

Bendamustine, active in multiple myeloma (MM), is a bifunctional mechlorethamine derivative with alkylating properties. Bortezomib, approved to treat MM, is effective in combination with alkylators. The tolerability and efficacy of bendamustine plus bortezomib in relapsed/refractory MM was assessed in an open‐label, dose‐escalating, phase I/II study. Patients aged ≥18 years received intravenous bendamustine 50, 70, or 90 mg/m² (days 1 and 4) plus bortezomib 1·0 mg/m² (days 1, 4, 8, and 11) for up to eight 28‐day cycles. No dose‐limiting toxicity was observed after cycle 1; bendamustine 90 mg/m² plus bortezomib 1·0 mg/m² was designated the maximum tolerated dose (MTD). The most common grade 3/4 adverse events were leucopenia (58%), neutropenia (50%), lymphopenia (45%), and thrombocytopenia (30%). Primary efficacy measure was overall response rate (ORR), which was the combined complete response (CR), very good partial response (VGPR), partial response (PR), and minimal response (MR). ORR was 48% (one CR, two VGPR, nine PR, and seven MR) for all 40 enrolled patients, 52% (16/31) at the MTD (90 mg/m²), and 42% and 46% for prior use of bortezomib (n = 31) or alkylators (n = 28) respectively. Bendamustine plus bortezomib was well tolerated with promising efficacy in this heavily pretreated population.     

A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide‐containing regimens

Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open‐label, single‐institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide‐refractory patients. Patients were considered lenalidomide‐refractory if they had no clinical response (<minimal response) on a previous lenalidomide‐containing regimen (lenalidomide non‐responsive) or if they had progressive disease on or within 60 days of discontinuing a previous lenalidomide‐containing regimen (lenalidomide relapsed/refractory). Patients received oral vorinostat 400 mg days 1–7 and 15–21, lenalidomide 25 mg days 1–21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28‐day cycles. Twenty‐five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression‐free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre‐treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide‐refractory patients.     

Phase I‐II trial of oral cyclophosphamide,prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma

This single institution, open label Phase I‐II dose escalation trial evaluated the safety and efficacy of the combination of lenalidomide (Revlimid®), cyclophosphamide and prednisone (CPR) in patients with relapsed/refractory multiple myeloma. The maximal administered dose of CPR consisted of cyclophosphamide 300 mg/m² on day 1, 8, and 15, lenalidomide 25 mg on d 1–21 and prednisone 100 mg every other day in a 28‐d cycle. Between November 2007 and June 2009, 32 patients were entered in cohorts of three at three dose levels. The median age was 64 years, 59% were male, with a median two prior regimens. Responding patients could stay on treatment until progression. The full‐dose CPR regimen produced no dose‐limiting toxicity and was delivered for a median of 16 months (3·5–65 months) with acceptable safety and tolerance. The overall response rate (≥ partial response) was 94% at a median follow up of 28 months. The median progression‐free survival was 16·1 months [95% confidence interval (CI); 10·9–22·5 months], while the median overall survival was 27·6 months (95% CI; 16·8–36·6 months). Only the beta‐2 microglobulin level at protocol entry correlated with a better survival (P = 0·047). These observations compare favourably with other 2‐ and 3‐ drug combinations for relapsed/refractory myeloma, and suggest that CPR should be evaluated further in the setting of relapsed/refractory disease, or in newly diagnosed patients.     

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study

The combination of lenalidomide-dexamethasone is active in multiple myeloma (MM). Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells to lenalidomide and dexamethasone, providing the rationale for this Phase I, multicentre, single-arm study to assess the safety and determine the maximum-tolerated dose (MTD) of perifosine-lenalidomide-dexamethasone in relapsed and relapsed/refractory MM. Patients received escalating doses of perifosine 50-100 mg daily and lenalidomide 15-25 mg once daily on days 1-21 of each 28-d cycle, plus dexamethasone 20-40 mg weekly thereafter, as indicated. Thirty-two patients were enrolled across four dose cohorts. MTD was not reached, with 31 patients evaluable for safety/tolerability. The most common all-causality grade 1-2 adverse events were fatigue (48%) and diarrhoea (45%), and grade 3-4 neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). Among 30 evaluable patients, 73% (95% confidence interval, 57·5-89·2%) achieved a minimal response or better, including 50% with a partial response or better. Median progression-free survival was 10·8 months and median overall survival 30·6 months. Response was associated with phospho-Akt in pharmacodynamic studies. Perifosine-lenalidomide-dexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory MM.     

Phase II study of bendamustine,bortezomib and dexamethasone (BBD) in the first‐line treatment of patients with multiple myeloma who are not candidates for high dose chemotherapy

The combination of bendamustine, bortezomib and dexamethasone (BBD ) was evaluated as a first‐line therapy for multiple myeloma. The original treatment regimen of bendamustine 80 mg/m², days 1, 4; bortezomib 1·3 mg/m², days 1, 4, 8, 11; dexamethasone 40 mg, days 1, 2, 3, 4 on a 28‐day cycle (up to 8 cycles) was efficacious but determined relatively toxic in an interim analysis. The regimen was amended to bendamustine 80 mg/m², days 1, 2; bortezomib 1·3 mg/m², days 1, 8, 15; dexamethasone 20 mg, days 1, 2, 8, 9, 15, 16 every 28 days (up to 8 cycles), then maintenance 1·3 mg/m² IV bortezomib every 2 weeks. Fifty‐nine patients were enrolled. Primary endpoint was complete response (CR) rate. The original schema was given for a median of 7 cycles (range 1–8); modified schema was given for a median of 8 cycles (range 1‐8) plus maintenance. Overall response was 91%, CR was 9%. Median follow‐up was 19·1 months; median progression‐free survival was 11·1 months and 18·9 months on the original and modified regimens, respectively. The most common Grade 3/4 adverse events were fatigue and neuropathy. The combination of BBD is tolerable and efficacious in this patient population. Modifications to decrease intensity but increase duration translated to better outcomes.     

Outcomes in patients with relapsed or refractory multiple myeloma in a phase I study of everolimus in combination with lenalidomide

Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, has been studied in multiple myeloma (MM) but lacks significant single agent activity. Based on preclinical studies showing synergistic activity of mTOR inhibitors with lenalidomide, we studied the combination of lenalidomide and everolimus in relapsed or refractory MM in a phase I clinical trial. We assessed patient samples using gene expression, Western blotting and immunohistochemistry to probe the mTOR pathway. Twenty‐six patients were evaluable for toxicity. Dose‐limiting toxicities included grade 4 neutropenia and thrombocytopenia. The maximum tolerated dose was lenalidomide 15 mg and everolimus 5 mg for 21 d with a 7 d rest period. Grade 3/4 adverse events included thrombocytopenia (35%) and neutropenia (42%). The overall response rate was 65% (1 complete response + 4 partial response + 10 minimal response). The median progression‐free survival was 5·5 months and median overall survival was 29·5 months. Biomarker data demonstrated downregulation of phosphorylated p70S6K. Gene expression profiling suggested activation of mTOR in responders versus non‐responders. The combination of lenalidomide and everolimus was well tolerated with predictable toxicities and showed responses in a heavily pretreated population. When confirmed with larger patient numbers, this analysis may guide patient selection for future clinical trials of mTOR inhibition in MM.     

Low-dose lenalidomide and dexamethasone combination treatment in elderly patients with relapsed and refractory multiple myeloma

Objective: This study investigated the efficacy and safety of low-dose lenalidomide combined with dexamethasone in elderly patients with relapsed and refractory multiple myeloma (MM).

Methods: Thirty-two elderly patients with refractory and recurrent MM (median age: 64 years) were treated with low-dose lenalidomide (LD-R) combined with dexamethasone (D). LD-R (10?mg/d) was administered orally for 21 days and D (40?mg/d) was administered twice a day on days 1–4, 9–12, and 17–20. The treatment lasted 2–8 28-day cycles.

Results: After two cycles, the complete, very good partial, and partial remission rates were 12.5% (4/32), 25.0% (8/32), and 34.4% (11/32), respectively. The overall response rate was 71.9% (23/32). After a 24-month follow-up, 23 patients responded to therapy, three were in complete remission, four were stable, and 16 exhibited disease progression. In addition, median time-to-progression was 13 months. Observed side effects were hypodynamia, gastrointestinal reaction, peripheral neuritis, and mild hypocytosis.

Conclusion: Low-dose lenalidomide in combination with dexamethasone is an effective and safe treatment for relapsed and refractory MM in elderly patients.     

A phase 2 study of modified lenalidomide,bortezomib and dexamethasone in transplant‐ineligible multiple myeloma

We sought a regimen that incorporates optimal novel agents and balances efficacy with toxicity in transplant‐ineligible multiple myeloma (MM) patients. Our study evaluated modified lenalidomide‐bortezomib‐dexamethasone (RVD lite) in this population and was administered over a 35‐day cycle. Lenalidomide 15 mg was given orally on days 1–21; bortezomib 1·3 mg/m² weekly subcutaneously on days 1, 8, 15 and 22; and dexamethasone 20 mg orally was given on the day of and day after bortezomib for 9 cycles followed by 6 cycles of consolidation with lenalidomide and bortezomib. The primary objective was to evaluate the overall response rate (ORR); secondary objectives included safety, progression‐free survival (PFS) and overall survival (OS). Fifty‐three eligible patients were screened between April 2013 and May 2015; 50 received at least one dose of therapy. Median age at study entry was 73 years (range 65–91). The ORR was 86% and 66% of patients achieved a very good partial response or better. Median PFS was 35·1 months (95% confidence interval 30·9–not reached) and median OS was not reached at a median follow‐up of 30 months. Peripheral neuropathy was reported in 31 (62%) patients with only 1 patient experiencing grade 3 symptoms. RVD lite is a well‐tolerated and highly effective regimen, with robust PFS and OS, in the transplant‐ineligible MM population.     

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first‐in‐class, once‐daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low‐dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2‐stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0–14·7). Progression‐free survival was 4·6 months (range, 0·4–17·3). Grade 3–4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3–4 non‐haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre‐treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment.     

Upfront lower dose lenalidomide is less toxic and does not compromise efficacy for vulnerable patients with relapsed refractory multiple myeloma: final analysis of the phase II RevLite study

The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment. The overall response rate was 71% (complete response 15%). Median (range) progression‐free survival (PFS) and overall survival (OS) were 8·9 (6·9–11·5) and 30·5 (20·0–36·2) months, respectively. Upon formal statistical comparison of these endpoints to that of a matched cohort of patients from the pivotal phase III MM009/MM010 studies who received standard‐dose lenalidomide (25 mg) and high‐dose dexamethasone (40 mg) no difference was seen in PFS (P = 0·34) and OS (P = 0·21). Importantly, grade 3–4 toxicities were reduced with low‐dose lenalidomide, mainly lower neutropenia (29% vs. 41%), infections (23% vs. 31%) and venous thromboembolism (3% vs. 13%). This study supports a strategy of lenalidomide dose reduction at the outset for at‐risk patients, and prospectively confirms that such an approach reduces adverse events while not compromising patient response or survival outcomes.     

A sequential cohort study evaluating single-agent KappaMab and KappaMab combined with lenalidomide and low-dose dexamethasone in relapsed and/or refractory kappa light chain-restricted multiple myeloma (AMaRC 01-16)

KappaMab (KM; formerly MDX-1097) is a monoclonal antibody specific for the kappa myeloma antigen (KMA), a cell-surface antigen expressed on malignant plasma cells in kappa-restricted multiple myeloma (κMM), some lymphomas, occasional tonsillar B cells and in vitro activated B cells, but not on normal B cells in bone marrow. Phase I/IIa studies of single-agent KM confirmed a favourable toxicity profile and evidence of anti-myeloma activity. Ex-vivo studies demonstrating upregulation of KMA by lenalidomide, and enhanced effector-cell cytotoxicity provided the rationale for this phase IIb study where KM or KM in combination with lenalidomide and dexamethasone (KM-Rd) was administered in relapsed, refractory κMM patients. In addition, outcomes for a real-world matched case–control cohort from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) who received Rd were compared to the KM-Rd cohort. KM-Rd demonstrated an overall response rate of 82.5% which compared favourably to the Rd-MRDR cohort of 45.1%. Both single-agent KM and KM-Rd regimens were well tolerated, with the KM-Rd safety profile similar to patients given only Rd in other clinical settings. Based on the excellent safety profile and significant efficacy, further clinical trials escalating the KM dose and pairing KM with other standard-of-care treatments are planned.     

Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma

Background

This retrospective pooled analysis of two phase III trials (MM-009/MM-010) compared clinical outcomes of patients who achieved a complete response or very good partial response to treatment with lenalidomide plus dexamethasone with the outcomes of those who only achieved a partial response.

Design and Methods

Patients (n=353) received lenalidomide (25 mg/day for 21 days of each 28-day cycle) plus dexamethasone (40 mg on days 1–4, 9–12, and 17–20 for four cycles, and only on days 1–4 after the first four cycles). Time to response, duration of response, time-to-progression, overall survival, and adverse events were investigated for patients who had a complete or very good partial response and compared with those of patients who had a partial response.

Results

At the time of unblinding, 32% of patients had achieved a complete or very good partial response and 28% had a partial response. Half (50.5%) of the patients who had a partial response as their initial response achieved a complete or very good partial response with further treatment. The probability of achieving a complete or very good partial response with continued lenalidomide treatment decreased with delayed achievement of a partial response (by cycle 4 versus later); however, it remained clinically significant. With an extended follow-up of 48 months, the median response duration, time-to-progression, and overall survival were longer in patients with a complete or very good partial response than in those with a partial response (24.0 versus 8.3 months, P<0.001; 27.7 versus 12.0 months, P<0.001; not reached versus 44.2 months, P=0.021, respectively). The benefit of a complete or very good partial response was independent of when it was achieved.

Conclusions

Continuing treatment with lenalidomide plus dexamethasone to achieve best response, in the absence of disease progression and toxicity, provided deeper remissions and greater clinical benefit over time for patients in this study.     

Continuous treatment with lenalidomide and low‐dose dexamethasone in transplant‐ineligible patients with newly diagnosed multiple myeloma in Asia: subanalysis of the FIRST trial

The phase 3 FIRST (Frontline Investigation of REVLIMID + Dexamethasone Versus Standard Thalidomide) trial demonstrated that lenalidomide plus low‐dose dexamethasone (Rd) until disease progression (Rd continuous) is an effective treatment option for transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). Given genetic differences between Asian and Western populations, this subanalysis of the FIRST trial examined the safety and efficacy of Rd (given continuously or for 18 cycles [Rd18]) and MPT (melphalan, prednisone, thalidomide) in 114 Asian patients from Mainland China, South Korea and Taiwan. Efficacy and safety with Rd continuous in Asian patients were consistent with those in the overall study population. The overall response rates were 77·8% for Rd continuous, 57·5% for MPT and 65·8% for Rd18. The risk of progression or death was reduced by 39% with Rd continuous versus MPT and by 35% with Rd continuous versus Rd18. Rd continuous improved the 3‐year survival rate compared with MPT (70·2% vs. 56·4%) and Rd18 (58·1%). Common grade 3/4 adverse events in the Rd continuous and MPT arms were neutropenia (25·0% vs. 43·6%), infection (19·4% vs. 28·2%) and anaemia (19·4% vs. 15·4%), respectively. Thromboembolic event rates were low, and no second primary malignancies were observed. Rd continuous is safe and effective in transplant‐ineligible Asian patients with NDMM.     

Carfilzomib,lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study

A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression‐free survival (PFS ) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM ). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio (HR ), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group (HR , 0·753). For patients <70 years the overall response rate (ORR ) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib‐lenalidomide‐dexamethasone has a favourable benefit‐risk profile for patients with RMM , including elderly patients ≥70 years old. Trial Registration: clinicaltrials.gov identifier: NCT01080391.