Novel Agents Improve Outcomes as Maintenance Therapy for Multiple Myeloma
New York, NY—Maintenance therapy is now an option for the treatment of multiple myeloma in elderly patients and in patients who have undergone autologous stem-cell transplant (ASCT). Thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade) have all shown benefit in the maintenance setting, said Steven Devine, MD, Professor of Medicine and Director of the Blood and Marrow Transplant Program, Ohio State University Comprehensive Cancer Center,Columbus, during the recent National Com prehensive Cancer Net work (NCCN) 6th Congress on Hematologic Malignancies.
Dr Devine defined maintenance therapy as treatment designed to prevent relapse in patients who achieve complete response (CR) or partial response with induction therapy. Maintenance therapy for myeloma is usually of relatively low intensity and long duration, he said.
Maintenance therapy for myeloma continues to evolve as new agents become available. Selection of the best drug for particular patient groups is the subject of ongoing trials. At present, NCCN guidelines recommend thalidomide, lenalidomide, and bortezomib for maintenance therapy.
For maintenance, thalidomide has category 1 recommendation and bortezomib and lenalidomide have category 2A recommendation, but thalidomide carries a high risk for severe peripheral neuropathy.
Lenalidomide is now included in the NCCN guidelines as an option for patients with active myeloma who respond to induction therapy; these patients can either continue induction chemotherapy to plateau or undergo ASCT and then be treated with maintenance therapy. Lenalidomide as maintenance therapy is supported by two phase 3 trials (McCarthy PL, et al. Blood. 2010;116:abstr 37; Attal M, et al. Blood. 2010;116:abstr 310). Both studies showed that lenalidomide maintenance therapy doubled progressionfree survival (PFS) after ASCT from approximately 2 years to 4 years and numerically improved survival. Lenalidomide was generally well tolerated. Hematologic events were the most common side effects. A slight increase in secondary malignancies was reported in both studies, and patients are being monitored with this in mind.
“Evidence from these trials suggests that in contrast to thalidomide, lenalidomide maintenance therapy at doses of 5 to 15 mg/day is generally well tolerated. The intent should be to use it for at least 1 year,” said Kenneth C. Anderson, MD, Chief, Division of Hematologic Neoplasia, Director of the Jerome Lipper Multiple Myeloma Center, and Vice Chair of the Joint Program in Transfusion Medicine, at the Dana-Farber Cancer Institute.
Bortezomib maintenance therapy has also been studied, but the data are less mature. The Haemato Oncology Foundation for Adults in the Netherlands (HOVON) trial (Sonneveld P, et al. Blood. 2010;116: abstr 40) showed that bortezomib maintenance improved CR, near-CR, and partial response rates, as well as PFS and overall survival (OS) compared with thalidomide in newly diagnosed ASCT candidates. In contrast to lenalidomide, bortezomib appears to overcome poor-risk cytogenetic abnormalities, including 13q and 17p deletions.
For elderly patients who are transplant- ineligible, melphalan (Alkeran)/ prednisone (Deltasone)/lenalidomide (MPR) followed by lenalidomide maintenance is a good option. A phase 3 study showed that MPR plus lenalidomide maintenance versus MPR alone or melphalan/prednisone (MP) improved PFS from 14 months and 13 months with MPR and MP alone, respectively, to 31 months. No OS advantage has been reported yet. A low rate of secondary malignancies was seen in this trial.
Bortezomib-based induction therapy is another good option for elderly patients with newly diagnosed myeloma (Niesvizky R, et al. Blood. 2010; 116:abstr 619). In this study, 3 different bortezomib-based regimens were active, and bortezomib maintenance was well tolerated with increased rates of very good partial remission in all 3 arms.