Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance

Saad Z Usmani, Rachel Sexton, Antje Hoering, Christoph J Heuck, Bijay Nair, Sarah Waheed, Yazan Al Sayed, Nabeel Chauhan, Nisar Ahmad, Shebli Atrash, Nathan Petty, Frits van Rhee, John Crowley, Bart Barlogie, Saad Z Usmani, Rachel Sexton, Antje Hoering, Christoph J Heuck, Bijay Nair, Sarah Waheed, Yazan Al Sayed, Nabeel Chauhan, Nisar Ahmad, Shebli Atrash, Nathan Petty, Frits van Rhee, John Crowley, Bart Barlogie

Abstract

Thalidomide and lenalidomide constitute an important part of effective myeloma therapy. Recent data from the Intergroup Francophone du Myélome, Cancer and Leukemia Group B, and Gruppo Italiano Malattie Ematologiche dell Adulto MM-015 trials suggest that lenalidomide maintenance therapy is associated with a higher incidence of second primary malignancies (SPMs), including both hematologic and solid malignancies. In the present study, we analyzed data from the Total Therapy 2 (TT2) trial, along with the 2 Total Therapy 3 (TT3) trials. TT2 patients were assigned randomly to either a control group (no thalidomide) or to the experimental group (thalidomide during induction, between transplantations, and during consolidation and maintenance). The 2 TT3 trials used thalidomide and bortezomib during induction, before and in consolidation after tandem melphalan-based transplantation; TT3A applied VTD (bortezomib, thalidomide, dexamethasone) in the first year of maintenance and TD for 2 more years, whereas TT3B used VRD (bortezomib, lenalidomide, dexamethasone) maintenance for 3 years. The cumulative incidence of SPMs did not differ significantly among the TT trial components when measured from enrollment (P = .78) or from initiation of maintenance (P = .82). However, a pairwise comparison of the TT2 arms suggested a lower incidence of hematologic SPMs in the thalidomide maintenance arm (hazard ratio = 0.38; P = .09). These trials are registered at www.clinicaltrials.gov as NCT00573391 (TT2), NCT00081939 (TT3A), and NCT00572169 (TT3B).

Figures

Figure 1
Figure 1
Timing of onset of all SPMs in TT2, TT3A, and TT3B. From enrollment (A) and from maintenance (B).
Figure 2
Figure 2
Timing of onset of solid-tissue SPMs in TT2, TT3A, and TT3B. From enrollment (A) and from maintenance (B).
Figure 3
Figure 3
Timing of onset of hematologic SPMs in TT2, TT3A, and TT3B. From enrollment (A) and from maintenance (B).

Source: PubMed

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