Selinexor in Combination with Standard or Reduced-Dose Melphalan Conditioning Regimen for Autologous Stem Cell Transplantation in Multiple Myeloma
Authors: Shuai Su , Xu Bin , Li Chunrui , Wang Di , Tong Xiwen , Zhu Yi , Mao Xia , Xiao Min , Zhang Donghua 
Published: December 2024

Background:

Melphalan, 200mg/m2, is recommended by the National Comprehensive Cancer Network (NCCN) guideline as the standard conditioning regimen for autologous stem cell transplantation (ASCT) in young newly diagnosed multiple myeloma (NDMM) patients. Reduced-dose melphalan is recommended for patients with complications such as renal dysfunction or advanced age. However, dosage reduction implies decreased efficacy. Selinexor is an orally administered nuclear export inhibitor approved for relapsed/refractory MM, which is easy to take and kidney-safe. Therefore, we combined selinexor with melphalan as a new conditioning regimen in MM patients.

Aims:

We aim to evaluate the efficacy and safety of combining selinexor with melphalan as a conditioning regimen for ASCT in patients with MM.

Methods:

From April 2023 to July 2024, 7 patients diagnosed with MM undergoing ASCT were included. The regimen included selinexor 60mg/day orally on days -10 and -3, along with standard or reduced-dose melphalan administered on day -2. Maintenance therapy after ASCT with selinexor at 20-40mg/day once weekly was offered based on patient preference and tolerance. The primary endpoints were progression-free survival (PFS) and safety, with secondary endpoints including complete remission (CR) conversion rate, the negative rate of MRD, overall survival (OS), and the rate of renal function improvement.

Results:

The median age of the 7 patients was 53 (range 46-60), with a male-to-female ratio of 3:4. IgG subtype was observed in 3 patients, IgA in 1, and light chain subtype in 3. 4 patients were classified as high-risk and 3 as intermediate-risk. 1q21 amplification was detected in 3 patients. All patients received bortezomib-based induction chemotherapy, with a median of 9 cycles (range 5-13). Disease status pre-transplant was listed as follows: CR in 3 patients, VGPR in 2, PR in 2, MRD-negative in 1, and MRD-positive in 6. 4 patients with renal dysfunction received reduced-dose melphalan (100-180mg/m2). 2 patients received reduced-dose melphalan (140-160mg/m2) due to weak physical condition, and 1 young patient without any complications received standard-dose melphalan (200mg/m2). Patients received a median of 4.68 (range 2.67-6.80) *10^6/kg CD34+ cells. Neutrophil and platelet engraftment occurred at a median of 13 days (range 11-15) and 15 days (range 11-16), respectively. Post-transplant responses were CR in 6 patients and PR in 1, resulting in a CR conversion rate of 75%. Post-transplant MRD was evaluable in 3 patients, with 2 negative and 1 positive. No worsening of renal dysfunction was observed. Among the 4 patients with renal dysfunction, 1 achieved minor improvement in renal function post-transplant. No severe adverse events occurred. Treat-related adverse events included febrile neutropenia observed in 3 patients, nausea in 5, vomiting in 4, oral mucositis in 3, pulmonary infection in 1, hypokalemia in 4, and hyponatremia in 6. 3 patients began maintenance therapy with selinexor after ASCT, 1 of whom temporarily discontinued due to bone marrow suppression. 2 patients received lenalidomide, and 1 received pomalidomide as maintenance therapy. Another 1 patient has not yet started maintenance therapy. As of July 22, 2024, no disease progression or deaths were observed among the patients with a median follow-up of 3 months (range 2-15).

Conclusion:

The combination of selinexor and melphalan as a conditioning regimen for MM patients undergoing ASCT is effective and safe. Further exploration of melphalan dosage for special populations (those with complications or advanced age) is warranted.