BOSTON – While treatment of and survival with multiple myeloma has dramatically improved with better therapeutic options, concerns have been raised about a concurrent increase in second primary malignancies that appear to be related to treatment.

A presentation at the 61st American Society of Hematology Annual Meeting and Exposition in Orlando cited a Swedish study that suggested an increased risk of developing acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in MM patients (11.51 fold), along with 1.19-fold increased risk of non-hematologic malignancies.1

“However, it is presently unclear whether this increase is related to therapy or other factors such as host, environment or behavioral patterns,” according to the study team, led by the Dana-Farber Cancer Institute and involving the VA Boston Healthcare System and the Michael E. DeBakey VA Medical Center in Houston.

The researchers sought to determine incidence of second primary malignancies and possible association with demographics, exposure, and therapy in a large population of patients treated by the VA healthcare system.

To do that, they used the VA’s nationwide Corporate Data Warehouse to identify patients diagnosed with multiple myeloma  from 1999 to 2017 and captured information on their age, race, therapy at induction, stem-cell transplant status, and exposure status. For each patient, the study team identified the first secondary primary malignancy after multiple myeloma treatment initiation, using the VA Central Cancer Registry. Excluded were patients who had records of malignancies prior to MM treatment initiation.

With 14,261 patients meeting the inclusion criteria, 552 (3.9%) were found to have had SPMs, consistent with prior literature. Median age at MM diagnosis was 69.22 years overall (95% CI 51.98-84.76), but slightly younger, 66.7 years (52.03-83.86),  for those with SPM, and 69.32 years (51.99-) for those without SPM. Median age at diagnosis of SPM was 70.2 years (55.43-86.75). The study noted that median time from MM treatment initiation to SPM was 2.38 years (0.09-9.37).

Of the 552 observed SPMs, 69 (12.4%) were hematologic (25 MDS, 19 lymphoma, 15 acute leukemia, 6 chronic leukemia, 4 MPN) while 84.5% (466) were oncologic, with prostate cancer the most common SPM (n=125, 22.6%).

“We did not observe statistically significant differences in incidence of SPM by smoking status (4.1% among current/former smokers vs 3.7% among never smokers; P=0.347), or Agent Orange exposure (4.2% among those exposed vs 3.8% among those not exposed; P=0.476),” the authors wrote.

The study also examined the relationship of common treatments to SPM, determining that identification of a secondary primary malignancy was more common among those exposed to lenalidomide (4.3% vs 3.4%, p=0.003), bortezomib (4.8 vs 3.3%, p<0.001), and transplant (7.5% vs 3.5%, p<0.001).

“Considering only therapy at induction, SPMs occur among 3.3% of those receiving lenalidomide/dexamethasone (Rd), 4.0% of those receiving bortezomib/dexamethasone (Vd), and 4.5% of those receiving RVd (p=0.11),” the researchers stated. “Among those who also received transplant, SPM occurs in 6.0%, 6.6%, and 8.7% of those receiving Rd, Vd, and RVd, respectively (p=0.49). And, among those who did not receive transplant, SPM occurs in 3.1%, 3.5%, and 3.7% of cases, respectively (p=0.52).”

The authors added that, compared to data from the VA Central Cancer Registry on cancer incidence at the VA in general, the incidence of SPM (3.9%) among multiple myeloma patients is substantially higher than the overall incidence of malignancy in the VA (0.78%).

“Moreover, we find that common risk factors for developing malignancy, including smoking status and exposure to Agent Orange, are not significantly associated with developing SPM after MM diagnosis,” the researchers wrote. “In contrast, we find that therapy utilization, particularly transplant, is associated with significant increases in susceptibility to SPM. Better understanding of these risk factors is needed to appropriately assess the tradeoff of decreased myeloma-related mortality, but potentially increased risk of secondary malignancies with common myeloma therapy options.”

  1. Fillmore N, Yellapragada SV, Yildirim C, Afrough A. et al. Incidence of Second Primary Malignancies and Association with Treatment in US Veterans with Multiple Myeloma. Presented at the 61st American Society of Hematology Annual Meeting and Exposition; December 2019; Orlando, FL