Patterns of second primary malignancy risk in multiple myeloma patients before and after the introduction of novel therapeutics

Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance. ALL was unexpectedly diagnosed on bone marrow biopsy. One patient was diagnosed on routine biopsy performed as part of requirements of the clinical trial. Both patients had B-cell ALL, without known poor risk cytogenetics, and were managed with standard induction therapies resulting in complete remission. We also reviewed the literature for similar cases of secondary ALL (sALL) in MM patients exposed to immunomodulatory drugs (IMiDs). In conclusion, persistent cytopenias in responding MM patients receiving IMiDs maintenance should be an indication for bone marrow biopsy. Patients develop sALL after median of 32.5 months (range, 20–84) from being on lenalidomide or thalidomide maintenance, often presenting with cytopenias, display low tolerance to chemotherapy, but remission can often be achieved.

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Second primary malignancy after multiple myeloma-population trends and cause-specific mortality

British Journal of Haematology ◽

10.1111/bjh.15426 ◽

2018 ◽

Vol 182 (4) ◽

pp. 513-520 ◽

Cited By ~ 9

Author(s):

Luciano J. Costa ◽

Kelly N. Godby ◽

Saurabh Chhabra ◽

Robert Frank Cornell ◽

Parameswaran Hari ◽

...

Keyword(s):

Multiple Myeloma ◽

Population Trends ◽

Second Primary ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Specific Mortality

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A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide

Blood ◽

10.1182/blood-2011-08-373514 ◽

2012 ◽

Vol 119 (12) ◽

pp. 2764-2767 ◽

Cited By ~ 100

Author(s):

Meletios A. Dimopoulos ◽

Paul G. Richardson ◽

Nancy Brandenburg ◽

Zhinuan Yu ◽

Donna M. Weber ◽

...

Keyword(s):

Multiple Myeloma ◽

Pooled Analysis ◽

Second Primary ◽

Separate Analysis ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Pivotal Phase ◽

Refractory Multiple Myeloma ◽

Skin Cancers ◽

Second Primary Malignancies

Abstract In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory multiple myeloma (MM; N = 3846), the overall incidence rate (IR, events per 100 patient-years) of second primary malignancies (SPMs) was 3.62. IR of invasive (hematologic and solid tumor) SPMs was 2.08, consistent with the background incidence of developing cancer. In a separate analysis of pooled data from pivotal phase 3 trials of relapsed or refractory MM (N = 703), the overall IR of SPMs was 3.98 (95% confidence interval [CI], 2.51-6.31) with lenalidomide/dexamethasone and 1.38 (95% CI, 0.44-4.27) with placebo/dexamethasone; IRs of nonmelanoma skin cancers were 2.40 (95% CI, 1.33-4.33) and 0.91 (95% CI, 0.23-3.66), respectively; IRs of invasive SPMs were 1.71 (95% CI, 0.86-3.43) and 0.91 (95% CI, 0.23-3.66), respectively. The risk of SPMs must be taken into account before initiating lenalidomide treatment. In the context of the observed survival benefit in relapsed or refractory MM patients, the benefit/risk profile of lenalidomide/dexamethasone remains positive.

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