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Expert Point of View: Suzanne Lentzsch, MD, PhD


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IFM 2009 showed that autologous stem cell transplant (ASCT) combined with lenalidomide, bortezomib, and dexamethasone (RVd) results in a significantly better progression-free survival than RVd alone in newly diagnosed patients with myeloma.1 “The data favor immediate ASCT, as transplant resulted in a significant prolongation of progression-free survival by 1 year,” said Suzanne Lentzsch, MD, PhD, Professor of Medicine and Director of the Multiple Myeloma and Amyloidosis Service at Columbia University.

“As in many upfront trials, there was no ­difference in overall survival, mainly due to potent rescue treatments and a long overall survival in this disease, making it difficult to pinpoint the effects of the initial treatment,” Dr. Lentzsch acknowledged. She emphasized that the study found no increased rate of second primary malignancies. Fear of second primaries is a common reason for avoiding ASCT with high-dose melphalan, she added.

Suzanne Lentzsch, MD, PhD

Suzanne Lentzsch, MD, PhD

Supporting Evidence

Dr. Lentzsch pointed to two additional large, randomized trials presented at ASH 2020 that confirm the superiority of ASCT, as shown by IFM 2009. In the Forte trial, presented by Francesca Gay, MD, for the GIMEMA group, 315 newly diagnosed patients received carfilzomib, lenalidomide, and dexamethasone (KRd) plus ASCT or KRd alone for 12 months.2 KRd plus ASCT resulted in a significantly better progression-free survival (78% vs 66%), a benefit observed across all subgroups. Additionally, minimal residual disease negativity (105) was also significantly improved after ASCT (68% vs 54%; P = .02).

The third large, randomized trial, performed by the European Myeloma Network (EMN02/HO95) and presented at the ASH meeting by Michele Cavo, MD, further confirmed the superior role of ASCT.3 Newly diagnosed patients received three to four cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD) induction and were randomly assigned to four cycles of bortezomib, melphalan, and prednisone (VMP) vs single or double ASCT. At a median follow-up of 60.3 months, the progression-free survival was 56.7 months in the ASCT arm vs 41.9 in the non-ASCT arm (P = .0001). Overall survival was similar.

“In my opinion, those three trials provide convincing evidence that ASCT in newly diagnosed myeloma is superior to a non-ASCT approach and should be considered as the standard of care for these patients,” Dr. Lentzsch commented. “It is essential to point out that IFM 2009 has a long follow-up of 8 years and that all three trials showed a sustained progression-free survival advantage in all subgroups. Therefore, especially in the setting of high risk, newly diagnosed patients should undergo ASCT, as this patient population needs the most intense treatment.”

Despite these three trials confirming the benefit of ASCT, Dr. Lentzsch acknowledged that none included an anti-CD38 monoclonal antibody in their induction regimens. It is unknown, therefore, whether a more potent induction regimen leading to deeper remissions would abolish the effect of ASCT. “Hence, the question of whether an effective regimen such as daratumumab plus KRd, with intensive maintenance such as carfilzomib/lenalidomide (KR), will obviate the need for ASCT is still unanswered,” she added. 

DISCLOSURE: Dr. Lentzsch has served as a consultant for or received honoraria from Sorrento, Janssen, Celularity, GSK, Takeda, AbbVie, Sanofi, and Karyopharm and has an equity ownership or served on the board of directors for Caelum Biosciences.

REFERENCES

1. Perrot A, Lauwers-Cances V, Cazaubiel T, et al: Early versus late autologous stem cell transplant in newly diagnosed multiple myeloma. 2020 ASH Annual Meeting & Exposition. Abstract 143. Presented December 5, 2020.

2. Gay F, Musto P, Scalabrini DR, et al: Upfront autologous hematopoietic stem-cell transplantation improves overall survival in comparison with bortezomib-based intensification therapy in newly diagnosed multiple myeloma. 2020 ASH Annual Meeting & Exposition. Abstract 142. Presented December 5, 2020.

3. Cavo M, Gay F, Beksac M, et al: Survival analysis of newly diagnosed transplant-eligible multiple myeloma patients in the randomized Forte trial. 2020 ASH Annual Meeting & Exposition. Abstract 141. Presented December 5, 2020.


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