Research presented at the 51st Annual ASH Meeting explored optimal induction therapies for managing multiple myeloma and a potential first-line therapy for patients with non-Hodgkin lymphoma (NHL).
“Studies such as these are designed to improve the quality of evaluation, diagnosis, and treatment of various blood cancers,” said Richard A. Van Etten, MD, PhD, Director of Tufts Medical Center Cancer Center in Boston. “The results of these studies not only give hematologists a better understanding of disease progression, but also direct them to the measures that are safer and more effective in treating their patients.”
Novel Regimens in Elderly Multiple Myeloma Patients
Over the past few years, the treatment of elderly patients older than 65 years with multiple myeloma has changed, mainly due to the introduction of novel agents such as thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide (Revlimid). According to results from the Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone (VISTA) trial, the combination of bortezomib, melphalan (Alkeran), and prednisone is significantly superior to melphalan and prednisone alone, which has been the current standard of care for multiple myeloma patients who cannot receive a stem cell transplant. However, research has not yet confirmed whether an alkylating agent or an immunomodulatory therapy is the optimal partner for bortezomib.
Researchers from the Spanish Myeloma Group designed a study to better determine if melphalan or thalidomide should be used as part of induction therapy in combination with bortezomib. The study showed that elderly patients were able to receive less aggressive treatment regimens of induction therapy by supplementing them with a maintenance treatment (abstract 3).
In order to evaluate whether the induction therapy regimen could be further optimized by decreasing toxicity while maintaining efficacy, the intensity of both treatment regimens was reduced as compared with the VISTA regimen, but supplemented with maintenance therapy. In this study, 260 patients with a median age of 75 years were randomized to receive a modified induction schedule of six cycles of bortezomib, melphalan, and prednisone (VMP) or bortezomib, thalidomide, and prednisone (VTP) as induction therapy followed by maintenance therapy with bortezomib and thalidomide (VT) or bortezomib and prednisone (VP) for up to 3 years.
Study results indicate that modified induction schedules for both VMP and VTP were highly effective with similar overall response rates (80% for VMP and 81% for VTP) and complete remission rates (20% for VMP and 27% for VTP), but there was a clear difference in the toxicity profile of each group. In the VMP regimen there was a higher incidence of neutropenia and infections, but VTP resulted in the development of cardiac toxicity. The frequency of grade 3/4 peripheral neuropathy was 5% in the VMP group. Maintenance therapy with either VT or VP also markedly improved the quality of patient responses with a good safety profile, increasing complete response from 23% up to 42%, with no significant differences in response rates between the VT and VP treatment arms. In addition, both maintenance regimens resulted in an acceptable toxicity profile.
“Melphalan with prednisone has been the gold standard for the treatment of elderly multiple myeloma patients for the past 40 years, but novel combination therapies have emerged as superior options,” said lead author Maria-Victoria Mateos, MD, PhD, attending physician, hematology department at the Hospital Universitario de Salamanca in Spain. “In this study, we demonstrate that the combination of a reduced dosage for induction therapy followed by maintenance therapy may be a novel approach for treating this patient population.”
First-Line Treatment of Advanced Follicular, Indolent, and Mantle Cell Lymphomas
While the current standard of care for patients with NHL is CHOP (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristin [Oncovin], and prednisone) plus rituximab (Rituxan), it has been linked to high toxicity rates. However, promising results have been observed in two phase II studies evaluating a new combination treatment consisting of bendamustine (Treanda) plus rituximab in patients with relapsed/refractory indolent or mantle cell lymphoma. In order to further investigate the role of bendamustine and rituximab combination therapy, researchers from the German Study Group Indolent Lymphoma (StiL) initiated a multicenter, randomized, phase III study to compare the efficacy and safety of bendamustine plus rituximab vs CHOP plus rituximab as a potential first-line therapy for patients with follicular, indolent, and mantle cell lymphoma (abstract 405).
A total of 549 patients were randomized to receive one dose of rituximab (375 mg/m2) plus two doses of bendamustine (90 mg/m2) every 28 days or the standard CHOP regimen every 21 days for a maximum of six cycles. The types of NHL were equally distributed between the two treatment regimens (55% and 56% for follicular lymphoma, 18% and 19% for mantle cell lymphoma, and 27% and 24% for other indolent lymphomas, respectively). The primary objective of the study was to improve progression-free survival for patients with NHL.
Bendamustine and rituximab combination therapy significantly improved progression-free survival and complete remission rates while showing less toxicity as compared with the current standard treatment. The median progression-free survival for bendamustine and rituximab combination therapy was 54.8 months compared with 34.8 months for CHOP and rituximab combination therapy. The complete remission rate of 40.1% for bendamustine and rituximab combination therapy was significantly higher than the 30.8% achieved with CHOP and rituximab combination therapy. As predicted, a higher frequency of serious adverse events was seen with the CHOP and rituximab combination therapy, such as neutropenia (10.7% vs 46.5%) and leukocytopenia (12.1% vs 38.2%). The bendamustine and rituximab combination therapy was better tolerated by patients as evidenced by lower rates of treatment side effects such as hair loss (15% vs 62%), infectious complications (95 vs 121 patients), nerve damage (18 vs 73 patients), and episodes of inflammation in the mucous lining of the mouth (16 vs 47 patients).
“While the CHOP and rituximab combination is the current standard of care, it is frequently associated with serious adverse events and more side effects, as was further shown in this study,” said lead author Mathias J. Rummel, MD, PhD, head of the department for hematology at the University Hospital in Giessen, Germany. “These promising results suggest that the combination of bendamustine and rituximab has the potential to become the new standard, first-line treatment option for patients with these non-Hodgkin lymphoma entities.”