Autologous Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Therapies

Ricardo D. Parrondo, MD; Sikander Ailawadhi, MD; Taimur Sher, MD; Asher A. Chanan-Khan, MD; Vivek Roy, MD

Disclosures

J Oncol Pract. 2020;16(2):56-66. 

In This Article

Induction Therapy

Patients who undergo upfront ASCT receive induction therapy for four to six cycles before stem cell collection to reduce tumor burden, reverse end-organ damage, and improve the quality of the graft. The combination of VRD is the most preferred regimen in the United States for induction on the basis of its superior PFS (43 v 30 months; P = .0018), OS (75 v 64 months; P = .025), and depth of response (partial response or better in 82% v 72%; P = .02) compared with RD.[4] A retrospective study comparing V, cyclophosphamide (C) D, VD, RD, VRD, thalidomide (T) D, and vincristine, doxorubicin, and D induction therapies reported respective 5-year OS rates of 79.2%, 72.3%, 79.2%, 79.0%, 57.4%, and 63.4% (P < .001), respectively. In a multivariable analysis, VRD had superior OS compared with VCD (HR, 0.32; 95% CI, 0.10 to 0.88; P = .03) and VD (HR, 0.16; 95% CI, 0.04 to 0.52; P = .002).[20] In the IFM 2013–04 study, VTD induction followed by ASCT resulted in deeper hematologic responses and a superior overall response rate compared with VCD induction followed by ASCT.[21] As such, triplet regimens containing a proteasome inhibitor and an immunomodulatory agent are favored for induction therapy.

In patients with acute renal insufficiency at the time of diagnosis, lenalidomide-based induction is generally avoided. Such patients should be treated with VCD or VTD initially. They can later be transitioned to VRD in the outpatient setting with lenalidomide dose adjustment as needed due to its superior depth of response, PFS, and OS.[4,20] There is evidence that novel agents can improve poor prognosis associated with high-risk cytogenetics. Bortezomib was demonstrated to improve the poor prognosis associated with t(4;14) (37.7% of patients experienced progression in the VTD arm compared with 56.1% of patients in the TD arm; P = .0174), but it is unclear if the poor prognosis associated with del 17p is also improved.[22] Carfilzomib (K)-RD induction may provide a PFS benefit compared with RD on the basis of the findings of the ASPIRE trial, which demonstrated a PFS benefit of 23.1 months for KRD compared with 13.9 months for RD treatment (P = .08) in patients with relapsed high-risk MM, including those with del17p.[23] In a phase III study comparing ixazomib (I)-RD with RD in patients with relapsed/refractory MM, higher PFS was observed in the IRD arm in both standard-risk and high-risk cytogenetics patients, including those with del17p (21.4 months in the IRD arm compared with 9.7 months in the RD arm; HR, 0.60; 95% CI, 0.29 to 1.24).[24] Results of trials evaluating the addition of monoclonal antibodies to standard immunomodulatory agent– and proteasome inhibitor–based triplet induction therapies are beginning to be reported. Daratumumab (Dara)-VTD induction followed by ASCT and Dara-VTD consolidation resulted in superior MRD negativity rates (10−5; 64% v 44%; P > .0001) compared with VTD alone.[25] Dara-VRD induction followed by ASCT resulted in a 42.4% stringent complete response rate compared with 32% with VRD induction followed by ASCT.[26] Clinical trials are currently evaluating novel agent combination induction regimens (Table 2).

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