Noteworthy Research Spans Range of Malignancies

Maurie Markman, MD

Editor-in-Chief of OncologyLive

Senior vice president for Clinical Affairs and National Director for Medical Oncology Cancer Treatment Centers of America, Eastern Regional Medical Center

With more than 4200 abstracts, the American Society of Hematology’s 2011 annual meeting was filled with a tremendous quantity of highly provocative and paradigm-changing new information regarding the management, epidemiology, and basic biology of hematologic conditions, including malignant disease. While it is impossible to attempt in a short article to review the contents and impact of this large international meeting, this commentary will focus on several very interesting presentations that will surely stimulate highly clinically relevant discussion regarding disease management within the realm of the hematologic malignancies.

Risk of Second Cancers in MM Therapy Examined

It is well recognized that multiple myeloma (MM) itself and the therapy employed in the management of this cancer have the potential to be associated with second malignancies. In an effort to determine the magnitude of this risk, and any changes in such risk that may have resulted from the introduction during the past decade of increasingly effective antineoplastic strategies to treat the condition, investigators examined patients with MM contained within the large Surveillance, Epidemiology, and End Results database from the years 1973 to 2008.¹

Specifically explored was the relationship between the risks of developing a second cancer after a diagnosis of MM during particular time periods that corresponded to the introduction of novel therapeutic strategies (eg, thalidomide, bortezomib, lenalidomide). The primary endpoint in the analysis was the documentation of a second malignancy at least 2 years after the diagnosis of MM. The only secondary cancers excluded from this evaluation were in situ malignancies (other than bladder and breast) and myelodysplastic syndrome.

The analysis, which included more than 29,000 patients, found an association between the risk of secondary malignancies and older age, male sex, and previous radiation or surgery. The researchers also found a greater risk of a second cancer during the most recent time periods analyzed.

Although this report raises the question of the immunosuppressive effects of the recently introduced potent novel therapeutics and the potential risk of the development of an additional cancer, it is important to note that with more effective treatment, patients also live longer and are therefore at greater risk (due to length of survival) to experience such an unfortunate event. Further research into this question is clearly indicated and the long-term consequences of newer therapeutic agents need to be carefully monitored.

Rituximab antibodies (turquoise) bind to the CD20 cell-surface markers on B-cells.

Image courtesy of Roche

Maintenance Rituximab in Follicular Lymphoma Questioned

A second paper reported the results of a most interesting phase III randomized trial that the Eastern Cooperative Oncology Group conducted to examine the potential clinical utility of a maintenance approach employing rituximab to prevent subsequent disease progression in patients with low tumor burden follicular lymphoma.² The hypothesis supporting the conduct of this trial was that the administration of rituximab (on an every 3-mo schedule) following an initial response to the agent in this specific clinical setting might substantially delay the time to subsequent disease progression.

However, the trial failed to demonstrate a clinically meaningful benefit associated with the maintenance approach. In fact, at 3-year follow-up, while 95% of the patient population randomized to receive maintenance rituximab remained without the requirement for cytotoxic therapy, 86% of patients who did not receive maintenance remained in a similar state. And although this difference was statistically significant (P = .027), there was no observable difference in the health status of the patient populations or their overall quality of life. Further, the amount of treatment received by the maintenance group (and the cost of this therapy) was substantially greater than in the population observed until evidence of disease progression.

Peripheral Blood Stem Cells (PBSCs) vs Bone Marrow Transplants (BMTs) From Unrelated Donors

Outcomes at 2 y

PBSC

BMT

Overall survival, intent-to-treat

51% (45%-57%)

46% (40%-52%)

Overall survival, transplanted

52% (46%-58%)

48% (42%-54%)

Disease-free survival, transplanted

47% (40%-53%)

44% (38%-50%)

Relapse

28% (22%-34%)

28% (23%-34%)

Any chronic graft vs host disease

53% (45%-60%)

40% (33%-47%)

Adapted from Anasetti C, Logan BR, Lee SJ, et al. Increased incidence of chronic graft-versus-host disease (GVHD) and no survival advantage with filgrastim-mobilized peripheral blood stem cells (PBSC) compared to bone marrow (BM) transplants from unrelated donors: results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0201, a phase III, prospective, randomized trial. Blood. ASH Annual Meeting Abstracts. 2011;118(21): abstr 1.

No Superiority for Stem Cell Transplants From Unrelated Donors

Finally, investigators from the Blood and Marrow Transplant Clinical Trials Network reported the results of a phase III trial that specifically examined the utility of bone marrow versus filgrastim-mobilized peripheral blood stem cells in the management of unrelated high-dose chemotherapy transplant.³ Previously reported randomized trial data had revealed the superiority of a strategy that utilized peripheral progenitor cells in HLA-identical siblings (speed of engraftment, reduced incidence of relapse, and improved survival), but such data were not available for unrelated donor transplants.

In this report, the researchers failed to demonstrate any superiority for the filgrastimmobilized peripheral blood stem cell approach compared with the use of bone marrow as a source to reconstitute the hematopoietic cell population. Disease-free and overall survival were identical in the 2 study arms, as was the risk of acute graft-versus-host disease. Further, there was no statistically significant difference in nonrelapse mortality between the groups, although the incidence of chronic graft-versus-host disease and specifically extensive chronic graft-versus-host disease, was greater in the population receiving the filgrastim-mobilized precursor cells.

These somewhat surprising results emphasize the importance of conducting randomized phase III trials in specific clinical settings.

These somewhat surprising results emphasize the importance of conducting randomized phase III trials in specific clinical settings. In the absence of these highly relevant evidence-based data in this study, many likely would have assumed that the outcome observed in the HLA-identical patient population would have also been observed in the unmatched donor patient population.

References

1. Raghavendra M, Gundrum JD, Go RS. Risk of second cancers among multiple myeloma (MM) patients in the era of novel agents: analysis using the Surveillance, Epidemiology and End Results (SEER) Database. Blood. ASH Annual Meeting Abstracts. 2011;118(21): abstr 1859.
2. Kahl BS, Hong F, Williams ME, et al. Results of Eastern Cooperative Oncology Group protocol E4402 (RESORT): a randomized phase III study comparing two different rituxumab dosing strategies for low tumor burden follicular lymphoma. Blood. ASH Annual Meeting Abstracts. 2011;118(21): Late-breaking abstr 6.
3. Anasetti C, Logan BR, Lee SJ, et al. Increased incidence of chronic graft-versus-host disease (GVHD) and no survival advantage with filgrastim-mobilized peripheral blood stem cells (PBSC) compared to bone marrow (BM) transplants from unrelated donors: results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0201, a phase III, prospective, randomized trial. Blood. ASH Annual Meeting Abstracts. 2011;118(21): abstr 1.