High-Dose Dexamethasone Reduces Bortezomib-Induced Thrombocytopenia.

Introduction: Bortezomib (B)-induced thrombocytopenia is a well documented adverse event; platelet nadir occur typically around day 10–12 of B therapy. The exact mechanism remains unknown but is not associated with reduced/abnormal marrow megakaryocytes. We postulated that corticosteroids could modulate the impact of B on the platelet budding, release or survival.

Method: A retrospective analysis was performed on patients with relapsed or refractory multiple myeloma, treated with B (1.3mg/m2 IV bi-weekly q3 weeks) ± Dex (20mg/d on day of, and day after, bortezomib) at our Institute between February 2005 to February 2007. Data was abstracted regarding patients’ baseline characteristics, platelet count at the beginning, at nadir, and the percentage of platelet reduction as well as the number of platelet transfusions with each treatment cycle. Comparisons of these parameters between the two groups were performed using the two-sample t-test.

Results: Forty one patients received a median of 4 cycles (range 1–10) of B ± D. Seven patients had dex only episodically with different cycles of B, and were excluded from analysis. Of the remaining 34 patients, 16 pts had a total of 75 cycles with dex, and 18 pts had a total of 65 cycles without dex. Baseline characteristics were similar in both groups including age, stage of disease, percentage of bone marrow plasma cell infiltration and mean platelet count prior to cycle 1 (196 × 109/l in the B+Dex group vs.160 × 109/l in the B without Dex group; p=0.27). Patients who received dexamethasone had a higher mean platelet count at the start of each new cycle (217 × 109/l vs. 171 × 109/l; p=0.002), a higher nadir platelet count (149 × 109/l vs. 88 × 109/l; p<0.001) and a lower mean platelet reduction (33% vs. 51%; p<0.001) per treatment cycle. Patients who did not receive dex required more platelet transfusions (p=0.004); on average 1 adult pool platelet per treatment cycle. Those who required transfusions had lower baseline platelets at the beginning of cycle 1.

Conclusion: Bortezomib induces a reduction of platelets by approximately 50% and concurrent Dex administration reduces both the incidence and depth of bortezomib-associated thrombocytopenia, resulting in a subsequent reduction in platelet transfusion requirements. We believe that dexamethasone is likely having an effect on either platelet release or survival through anti-apoptotic mechanisms at the megakaryocyte or platelet level, or by enhancing platelet survival. Clearly further studies are required to investigate the underlying mechanisms. We recommend the concurrent use of dexamethasone for patients with low baseline platelets being treated with bortezomib.