Reviewing the Latest Treatment Strategies in Patients with Transplant-Eligible Multiple Myeloma – Hematology Advisor

While multiple myeloma (MM) remains an incurable disease, anexpanding range of treatment options in the past decade has led to greaterlong-term survival in this patient population, with a reported increase from 3years previously to at least 7 to 10 years currently.1 Additionalgains are expected as novel therapies for MM continue to emerge. In a reviewpublished in the International Journal of Hematology, Kenshi Suzuki, MD,PhD, director ofMyeloma andAmyloidosis Center at the Japanese RedCross Medical Center in Tokyo, examined the evolving state of treatment fortransplant-eligible MM patients.1 Key points from the article arehighlighted below.

Induction Regimen

Greater response rates and progression-free survival (PFS) rates have been observed with triplet regimens containing immunomodulatory drugs and proteasome inhibitors compared with doublet regimens. In an open-label phase 3 trial (525 patients) published in 2017 in the Lancet, bortezomib-lenalidomidedexamethasone (VRd) was linked to significant improvements in median PFS (43 vs 30 months; stratified hazard ratio [HR], 0.712; 96% CI, 0.56-0.906; one-sided P =.0018) and median overall survival (OS; 75 vs 64 months; HR, 0.709; 95% CI, 0.524-0.959; two-sided P =.025) compared to Rd.2

Among newly diagnosed patients, autologous stem celltransplantation (ASCT) following induction therapy is standard practice forthose who are physically fit and younger than 70 years.1 Highercomplete response (CR) rates (59% vs 48%; P =.03) and minimal residualdisease negativity (MRD) rates (79% vs 65%; P <.001) have been notedamong patients receiving ASCT compared with Vrd alone.

As stated in the review, high-dose melphalan followed byASCT has been linked with longer PFS and OS, as well as treatment-relatedmortality rates of less than 1%, and thus should be considered for all eligiblepatients.1 Study results indicate that early ASCT is associated withhigher rates of CR, MRD, and PFS compared with deferred ASCT. Furthermore,ASCT can be considered for salvage in fit patients if the interval between thefirst ASCT and relapse is 18months or more, Dr Suzuki wrote.

Post-Transplantation Consolidation/Maintenance Therapy

A 2018 study reported longer PFS (median 3.3vs2.6years, P <.0001) and OS (median 8.5 vs 6.3years; P<.0001) in patients who achieved CR within 1 year following diagnosis.3

To improve the outcome of ASCT, it is important toeradicate MM tumor cells through the synergistic immunological effects of ASCTand peri- and post-ASCT treatment, according to Dr Suzuki.1 In ourclinical practice, up-front ASCT is performed, followed by continuousmulti-consolidation/maintenance regimens until [MRD] is sustained for2years with DRd-Kd-EPd-Rd every 6months (b phase). Patients aresubsequently monitored for relapse or MRD resurgence before treatment is stopped.

AntiCD38monoclonal antibodies appear to have a synergistic effect with immunomodulatorydrugs, based on the upregulation of CD38 expression in MM cell lines bypomalidomide (Pom) and lenalidomide (Len). In the ongoing phase 3 MAIA trial,the risk of disease progression or death was 44% lower in newly diagnosed patientswith MM treated with daratumumab-Rd compared with Rd alone.4

In a phase 1b study of patients with relapsed or refractory MM (RRMM), single-agent isatuximab (Isa) demonstrated an overall response rate (ORR) of 24.3%, a median PFS of 3.7 months, and an OS of 18.6 months. Ongoing studies are investigating the use of Isa with pomalidomide/dexamethasone (Pd) in RRMM, and with VRd in newly diagnosed MM.1

Among other agents approved for RRMM, researchers found thatonce-weekly carfilzomib(K)-Rd (KRd) showed promising activity with an acceptable safety profilein patients with newly diagnosed MM and reduce[d] the burden on elderlypatients and those living far from hospitals.1 Elotuzumab (Elo) incombination with Pd (EPd) demonstrated an ORR of 53% vs 26% with Pd and wasfound to have a favorable safety profile. Patients with RRMM who receivedixazomib maintenance therapy after ASCT showed a 28% reduction in the risk ofprogression or death compared with placebo (median PFS, 26.5 vs21.3months).1

Other findings have shown prolonged PFS (median 11.2 vs7.1months, P <.0001) in patients with RRMM receiving bortezomib plus Pd (PVd) compared with Vd aftertreatment with 1 to 3 previous regimens including lenalidomide, and theefficacy and safety of oral Pom/CPA/Dex (PCd) in the first relapse followinglenalidomide and bortezomib has also been noted.1

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Reviewing the Latest Treatment Strategies in Patients with Transplant-Eligible Multiple Myeloma - Hematology Advisor

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