Retrospective Analysis of Thrombocytopenia in Relapsed Multiple Myeloma Patients

Despite improvement in patient (pt) outcomes in recent years, multiple myeloma (MM) remains incurable and nearly all pts relapse after initial response to therapy. With disease progression and cumulative exposure to chemotherapeutic agents, pts with relapsed MM frequently develop cytopenias that represent a significant clinical challenge. At present, management of high-grade thrombocytopenia at our institution consists of supportive platelet transfusions. We hypothesize that thrombocytopenia is a highly relevant variable in the overall management of relapsed MM. As there are currently no studies in the myeloma literature that assess the impact of thrombocytopenia, we conducted a retrospective, chart-review study to evaluate the impact of thrombocytopenia in relapsed MM.

Participants included all pts with relapsed and/or relapsed-refractory MM who participated in clinical trials at Dana Farber Cancer Institute from January 1, 2007 – December 31, 2009. Many pts participated in more than one clinical trial during this time period. In this analysis, therapy administered to a particular patient in the context of one clinical trial is referred to as a “treatment regimen.” The overall incidence of thrombocytopenia (platelet count < 150,000/mcl) at initiation of a treatment regimen was recorded. The incidence of severe thrombocytopenia (platelet count < 100,000/mcl and < 75,000/mcl) was also determined. Medical record data collected to assess the clinical impact of thrombocytopenia included the following variables: episodes of ≥ grade 3 thrombocytopenia, number of platelet transfusions per pt per month on clinical trial, treatment delays and treatment discontinuations due to thrombocytopenia, the occurrence of bleeding events, and overall survival on clinical trial therapy. Point estimates with exact binomial confidence intervals and median and range are used to describe the data. The differences in platelet transfusion requirements were assessed by the two-sided Wilcoxon rank sum test.

To date, data has been abstracted on 43 treatment regimens in 23 pts. Fifteen pts had previously undergone autologous stem cell transplantation (ASCT), including two who had undergone tandem auto-transplant. The overall incidence of thrombocytopenia (platelet count < 150,000/mcl) was 40% at time of treatment initiation. In 13 of the 43 (30%, 90% Confidence Interval (CI)) treatment regimens, the platelet count at time of treatment initiation was less than 100,000/mcl. The platelet count at time of treatment initiation was less than 75,000/mcl in 11 of 43 (25%, 90%CI) treatment regimens reviewed. Cases where the platelet count was ≤ 100,000/mcl at time of study entry, mean platelet transfusion requirement per 4-week time interval was 2.35 units, while in cases where the platelet count was ≥ 100,000/mcl, the mean platelet transfusion requirement was 0.20 units transfusions per 4 week period was needed (p <.0001). In 20 (47%, 90% CI) of the treatment regimens reviewed, bortezomib was part of the therapeutic regimen. Data revealed no significant difference in requirement for platelet transfusion between regimens that included bortezomib versus those that did not. Two pts experienced a bleeding event during their treatment regimens. The platelet count at the time of the bleeding events was 57,000/mcl and 154,000/mcl. Treatment was delayed for one pt due to thrombocytopenia, and two pts were removed from study due to thrombocytopenia. Overall rate of survival at 1-year among 23 pts assessed to date was 91%.

Thrombocytopenia is a common problem in this pt population, particularly in pts that begin treatment with a platelet count < 100,000/mcl. This results in increased platelet transfusions, which are associated with heightened cost of health care and risk of transfusion related toxicities (ex. platelet alloimmunization). Complications related to thrombocytopenia such as bleeding events and treatment discontinuation are relatively rare; this is likely due to routine use of platelet transfusion. Of note, the incidence of transfusion is likely underrepresented by this retrospective study because intact bone marrow function is an eligibility criterion for most clinical trials involving pts with relapsed MM. This data supports the need for improved therapies that minimize transfusion support in this population.

Richardson:Millennium:; Celgene:; Johnson & Johnson:; Novartis:; Bristol Myers Squibb:. Anderson:Celgene: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.