Patients with multiple myeloma (MM) who develop second primary malignancies (SPMs) after autologous hematopoietic stem cell transplant (auto-HSCT) have worse outcomes than patients who do not develop SPMs, according to findings published in Blood Advances.

SPMs, particularly second hematologic malignancies (SHMs), are associated with inferior progression-free survival (PFS) and overall survival (OS), researchers reported.

The researchers analyzed data from 3948 adults with MM who had a first auto-HSCT with melphalan conditioning between 2011 and 2018 and then received post-HSCT maintenance. The median age at transplant was 61 (range, 20-82) years.

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Ten percent of patients (n=404) had a prior malignancy, including 334 with a history of a solid tumor. Most patients went into transplant with a very good partial response (n=1542) or partial response (n=1517). Lenalidomide (alone or in combination) was the most commonly reported maintenance regimen (n=2836). The median follow-up was 37 months.

SPMs occurred in 4% of patients (n=175) overall, with solid tumors comprising 64% of new SPMs. Melanoma (19%) and genitourinary malignancies (18%) were the most commonly observed SPMs. The median time from auto-HSCT to SPM development was 33 months. 

Among the 63 patients who developed SHMs, 57% had myeloid malignancies, 5% had lymphoid malignancies, and 38% had SHMs not otherwise specified. The median time from auto-HSCT to SHM development was 35 months. 

At 3 years, the cumulative incidence of SPMs was 3.3%, the incidence of SHMs was 1.1%, and the incidence of therapy-related myeloid neoplasms was 0.7%. Among the 404 patients who had a history of prior malignancy at baseline, 31 developed another malignancy after auto-HSCT. The incidence of SPMs did not differ significantly according to maintenance regimen. 

At last follow-up, 16% of patients who did not develop an SPM had died, and MM was the most common cause of death (85%). The death rate was 38% among patients who developed an SPM and 54% among patients who developed an SHM. In both groups, MM was still the most common cause of death (42% and 53%, respectively), followed by SPM (30%) and SHM (18%).

Compared with SPM-free patients, those with SPMs had inferior PFS (hazard ratio [HR], 2.62; 95% CI, 2.03-3.38; P <.001) and OS (HR, 3.85; 95% CI 2.95-5.02; P <.001). Patients with SHMs had worse PFS (HR, 5.01; 95% CI, 3.41-7.37, P <.001) and OS (HR, 8.13; 95% CI, 5.67-11.65; P <.001) than SPM-free patients as well.

“[T]he development of SPM and SHM leads to a poor survival in MM patients and is an important survivorship challenge,” the researchers wrote. “Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Ragon BK, Shah MV, D’Souza A, et al. Impact of second primary malignancy post-autologous transplantation on outcomes of multiple myeloma: A CIBMTR analysis. Blood Adv. Published online February 24, 2023. doi:10.1182/bloodadvances.2022009138

This article originally appeared on Cancer Therapy Advisor