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Chemotherapy-free regimen shows favorable long-term safety, efficacy in Waldenström macroglobulinemia
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The use of bortezomib, dexamethasone and rituximab in patients with Waldenström macroglobulinemia appeared active and demonstrated a favorable long-term safety profile, according to long-term follow-up of a phase 2 clinical trial.
“Novel agents offer an opportunity to improve therapy of Waldenström macroglobulinemia, by targeting pathways of critical importance for the survival of lymphoplasmacytic cells. ... Thus, in 2006, we designed a large phase 2 study to evaluate the activity of the combination of bortezomib, dexamethasone and rituximab in previously untreated patients with symptomatic Waldenström macroglobulinemia,” Maria Gavriatopoulou, MD, PhD, of the department of clinical therapeutics at National and Kapodistrian University of Athens, School of Medicine in Greece, told HemOnc Today.
Bortezomib (Velcade, Millennium/Takeda) plus dexamethasone and rituximab (Rituxan; Genentech, Biogen), or BDR, is a chemotherapy-free, non–stem cell toxic regimen that has been associated with high response rates and long maintained remissions. Gavriatopoulou said rituximab has been widely used for the treatment of Waldenström's macroglobulinemia, with patients showing minimal toxicity. However, it is only associated with a moderate response when used as a monotherapy, so it is recommended as a base in fixed combination regimens. Further, bortezomib targets multiple pathways by inhibiting protein homeostasis within cancer cells.
Therefore, the researchers hypothesized that the combination of bortezomib and rituximab could enhance treatment activity for patients with Waldenström macroglobulinemia.
Fifty-nine patients received BDR for 23 weeks. The regimen consisted of a single 21-day cycle of 1.3 mg/m2 bortezomib alone (days 1, 4, 8 and 11), followed by 1.6 mg/m2 bortezomib weekly (days 1, 8, 15 and 22) for four additional 35-day cycles, along with 40 mg dexamethasone and 375 mg/m2 rituximab cycles two and five.
In the intention-to-treat analysis, 85% of patients responded to the regimen, of whom 3% had a complete response, 7% had a very good partial response, 58% had partial response and 17% had a minor response. The overall major response rate was 68%.
The median time to first response was 3 months and the median time to best response was 5 months. However, four patients who responded achieved their best response 6 months after therapy ended. The median duration of response for patients with at least partial response was 64.5 months after a minimum 6 years’ follow-up.
OS was 66% at 7 years and the median PFS was 43 months. Researchers reported 40 Waldenström macroglobulinemia–related deaths.
Forty-six percent of patients experienced peripheral neuropathy and 20% reported neurotic pain. No patient developed secondary myelodysplasia, whereas transformation to high-grade lymphoma occurred in three patients who also received chemoimmunotherapy after BDR therapy, Gavriatopoulou said.
“The long-term safety profile of BDR is favorable, with high probability of response to reintroduction of rituximab-based regimens at relapse,” Gavriatopoulou said. “Thus, BDR is a very active, fixed duration, chemotherapy-free regimen, inducing durable responses with a favorable long-term toxicity profile.” – by Melinda Stevens
For more information:
Maria Gavriatopoulou can be reached at Department of Clinical Therapeutics, National and Kapodistrian of Athens School of Medicine, 80 Vas. Sofias Ave, 115 28 Athens, Greece; email: mariagabria@gmail.com.
Disclosures: Gavriatopoulou reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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