During a debate held at the 2019 International Waldenstrom’s Macroglobulinemia Foundation (IWMF) Educational Forum on the merits and drawbacks of treating patients with Waldenstrom Macroglobulinemia with a fixed duration of chemoimmunotherapy involving the anti-CD20 antibody, rituximab, versus continuous treatment with the Bruton tyrosine kinase inhibitor, ibrutinib, an area of consensus was the importance of personalizing treatment decisions to account for patient comorbidities and lifestyles.
In presenting the case in favor of rituximab-based therapy (eg, bendamustine/rituximab or bortezomib/dexamethasone/rituximab) Edward Stadtmauer, MD of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, PA emphasized that this type of treatment is typically administered for only 4 to 6 months and, unlike ibrutinib, provides a treatment-free interval for many patients. “If disease progresses, you can take ibrutinib,” he noted.
Dr Stadtmauer further emphasized while both approaches are generally well tolerated, there are differences in their toxicity profiles. He cited ibrutinib-associated risks of grade 3 or higher atrial fibrillation and hypertension of 10% to 12% and 5% to 10%, respectively. In contrast, he noted the association of nausea, vomiting, and cytopenia with some rituximab-based regimens, as well as a substantial risk of neuropathy with intravenous (IV) administration of bortezomib/dexamethasone/rituximab.
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One of the key points made by Jorge Castillo, MD of the Dana-Farber Cancer Institute in Boston, MA in his presentation in favor of continuous therapy with ibrutinib was the convenience of a once daily oral therapy compared with IV administration of chemoimmunotherapy. He also commented on the small risk of secondary leukemia in patients receiving chemoimmunotherapy.
Dr Castillo further pointed out that while both approaches are associated with rapid, deep, long-lasting responses in a high percentage of patients, emerging evidence suggests that MYD88 and CXCR4 status may facilitate selection of those patients likely to achieve superior outcomes with ibrutinib
Nevertheless, the absence of randomized data comparing these 2 approaches in patients with Waldenstrom Macroglobulinemia was noted by both speakers.
In his summary statement, Dr Stadtmauer opined that “either approach can be very successful and if the disease progresses, the alternative approach can then be used.”
Both presenters concluded their talks by stressing the importance of patient-physician discussions to personalize treatment.
Reference
Stadtmauer E, Castillo J. Fixed duration versus continuous treatment debate for Waldenstrom’s Macroglobulinemia. Presented at: 2019 International Waldenstrom’s Macroglobulemia Educational Forum. June 7-9, 2019; Philadelphia, PA.
