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

Krishnan, A; Kapoor, Prashant; Palmer, J M; Tsai, N-C; Kumar, Shaji; Lonial, Sagar; Htut, M; Karanes, C; Nathwani, N; Rosenzweig, M; Sahebi, F; Somlo, G; Duarte, L; Sanchez, J F; Auclair, D; Forman, S J; Berdeja, J G

doi:10.1038/leu.2017.352

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Proteasome inhibitors, such as bortezomib, in combination with pomalidomide and dexamethasone, either as retreatment or in relapse, have been evaluated, as well as more recent proteasome inhibitors such as carfilzomib and ixazomib. [33][34][35][36] However, intertrial comparisons must be interpreted with caution because they may be biased by differences in patient populations and study design. Nevertheless, this combination may be an ideal backbone for future studies in conjunction with monoclonal antibodies such as the anti-SLAMF7 37 or the anti-CD38 monoclonal antibodies, daratumumab or isatuximab, 38,39 given its favorable safety profile and oral administration.…”

Section: Discussionmentioning

confidence: 99%

Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma

Garderet

Kuhnowski

Berge³

et al. 2018

Blood

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Abstract It is important to have an effective therapy for patients with multiple myeloma (MM) at first relapse, particularly if an autologous stem cell transplant (ASCT) is considered at this stage. This multicenter, phase 2 trial evaluated the efficacy and safety of weekly oral pomalidomide-cyclophosphamide-dexamethasone (PCD) in patients with MM in first relapse after treatment with lenalidomide-bortezomib-dexamethasone (RVD). All patients had received RVD as induction and consolidation therapy, plus lenalidomide maintenance for 1 year (arm A). Half had also received an ASCT after induction (arm B). At MM relapse, all patients received 4 oral cycles of pomalidomide 4 mg (days 1-21), cyclophosphamide 300 mg (days 1, 8, 15, and 22), and dexamethasone 40 mg (days 1-4 and days 15-18 of a 28-day cycle; PCD). Responding patients in arm A underwent ASCT and received 2 additional cycles of PCD, whereas those in arm B received 5 cycles of PCD. All patients received pomalidomide-dexamethasone maintenance until disease progression. Primary end point was partial remission or better after the initial 4 cycles of PCD. Responses were obtained in 82/97 (85%) patients evaluated: complete remission (n = 1; 1%), very good partial remission (n = 32; 33%), and partial remission (n = 49; 51%). Three patients (3%) had stable disease, and 6 (6%) had disease progression (6 response failures). Forty-five (94%) of the 48 patients in arm A underwent planned ASCT. PCD was effective therapy after first relapse with RVD. After 4 cycles, the rate of partial remission or better was 85%, and 94% of planned ASCTs were performed. Toxicity was mostly hematologic and manageable. This trial was registered at www.clinicaltrials.gov as #NCT02244125.

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Section: Discussionmentioning

confidence: 99%

Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma

Garderet

Kuhnowski

Berge³

et al. 2018

Blood

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“…IXA has been evaluated in combination with other IMIDs [LEN, pomalidomide (POM)] with an ORR of 48% in a single-arm study of IXA-POM-DEX and an ORR of 78% in the pivotal TOURMALINE-MM1 trial examining the IXA-LEN-DEX (IRd) triplet. 21,37 While demonstrably effective, the IXA combination used in TOURMALINE-MM1 imposes a significant potential economic burden. 38 Although IRd is approved for the treatment of MM in >60 countries, including the USA and European Union, it is not reimbursed in most countries leaving a large proportion of patients with MM globally without access to the combination.…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16‐02 trial

et al. 2021

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We evaluated the efficacy and tolerability of continuous ixazomib-thalidomide-dexamethasone (ITd: 4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly). A total of 39 patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years with one to three prior lines of therapy were enrolled from two tertiary centres in Victoria and South Australia, Australia. The overall response rate (ORR) was 56Á4% with a clinical benefit rate of 71Á8%. The median progression-free survival was 13Á8 months [95% confidence interval (CI) 8Á2-22Á2] and median overall survival was not reached. The median time to best response and duration of response was 3Á7 months (95% CI 2Á8-10Á5) and 18Á4 months (95% CI 10Á2-31Á0) respectively. Prior immunomodulatory drug (IMID) exposure was associated with a lower ORR (40% vs. 73Á7%, P = 0Á03). Survival outcomes in patients with prior proteasome inhibitor (PI) and/or IMID exposure were similar. Patients received a median (range) of 11 (1-31) cycles of therapy and six patients (15%) remained on therapy at the time of final analysis. Grade 3/4 haematological and non-haematological adverse events were reported in 7Á7% and 20Á6% of patients respectively. ITd dose reductions were required in 15Á4%, 48Á7% and 35Á9% of patients respectively. The present study demonstrates promising effectiveness and tolerability of ITd as an affordable all-oral PI-IMID approach for RRMM.

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“…Терапию в полных дозах получили 25 больных. ГО был достигнут у 68 % пациентов, ВБП составила 8,6 мес, ОВ в течение 1 года -82 % [17].…”

Section: иксазомиб + помалидомид + дексаметазонunclassified

Efficiency of pomalidomide therapy in patients with multiple myeloma refractory to lenalidomide

Рехтина

Mendeleeva

2019

Onkogematologiâ

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Currently, there has been a marked increase in the number of opportunities for relapsed and refractory multiple myeloma treatment due toemergence of new target drugs. These include pomalidomide, a 3rd generation immunomodulator capable of treating double refractory multiple myeloma (to lenalidomide and bortezomib). Efficacy and safety of pomalidomide combined with low doses of dexamethasone have beenestablished in MM-003 and STRATUS trials. The summary presents the data on opportunities to further enhance the efficacy of pomalidomide combined with other antitumor drugs in patients with relapsed and refractory multiple myeloma who previously received 4–5 lines of therapy. It has been shown that triplets based on pomalidomide and dexamethasone combined with cyclophosphamide, bendamustine, daratumumab, carfilzomib, elotuzumab are highly effective in double refractory multiple myeloma patients. A combination of pomalidomide with proteasome inhibitors is a promising treatment provided that there is no refractoriness to bortezomib.

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

Cited by 8 publications

References 16 publications

Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma

Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma

A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16‐02 trial

Efficiency of pomalidomide therapy in patients with multiple myeloma refractory to lenalidomide

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