“Another course of steroids?” was the response of one of my chronic immune thrombocytopenia (ITP) patients when I called to let him know that the sudden drop in his platelet count again would necessitate a course of steroids to slow down the immune destruction of his platelets. The management of chronic ITP, especially in adult patients who do not achieve a sustained response with multiple lines of therapies, poses a unique and time-sensitive challenge.
Rilzabrutinib, the newest addition to the bruton tyrosine kinase (BTK) inhibitor class, offers a promising solution to this patient population, who experience frequent bleeding episodes, profound fatigue, and impaired quality of life (QoL). The lack of a rapid, durable, and well-tolerated treatment has left a gap in effective disease management. Risk of bleeding — especially in patients complicated with multiple comorbidities and those who need elective and emergency surgery — remains challenging. By targeting BTK — a critical "key" in the signaling pathway of B cells — BTK inhibitors offer a strategic approach to disrupting pathological immune responses. In the context of ITP, BTK inhibitors may hold the next key to halting the dysregulated signals driving autoimmune platelet destruction.
At yesterday’s Plenary Scientific Session, David J. Kuter, MD, DPhil, from Massachusetts General Hospital and Harvard Medical School, shared the phase III findings from the LUNA 3 trial evaluating rilzabrutinib in chronic ITP. The results herald the significant promise of a novel agent for the treatment of this debilitating disease, thereby addressing a much-recognized unmet clinical need.
Why Rilzabrutinib Matters
The multicenter, randomized, placebo-controlled LUNA 3 study enrolled 202 adult patients with chronic or persistent ITP who had platelet counts below 30×10⁹/L and a history of insufficient response to standard therapies. Half of the participants had undergone five or more prior treatments, with 28% requiring splenectomy.
“Some patients with ITP develop thrombocytopenia which is refractory to current treatments and are at high risk for bleeding and reduced quality of life,” said Dr. Kuter. “The novel BTK inhibitor rilzabrutinib was shown in this study to elevate and maintain a hemostatic platelet count in 23% of patients compared with 0% of those receiving placebo. Responding patients had a rapid rise in platelet count by day 15, had less bleeding, and experienced a marked reduction in their fatigue, with few low-grade side effects.” This rapid effect is crucial for mitigating bleeding risks. Patients also reported clinically meaningful improvements in fatigue, as measured by the ITP-Patient Assessment Questionnaire.
Safety and Tolerability
Safety is a critical factor in the adoption of novel therapies, particularly for chronic conditions like ITP. The most common adverse effects associated with rilzabrutinib include diarrhea (23%), nausea (17%), headache (8%), and abdominal pain (6%). These side effects were manageable and did not lead to a significant discontinuation rate, but investigators noted two serious adverse events. One rilzabrutinib-treated patient experienced a grade 3 peripheral embolism considered treatment-related, while another patient died from pneumonia unrelated to the drug. The high compliance rate across both treatment arms (>98%) reflects the feasibility of integrating rilzabrutinib into routine clinical practice.
Global Implications
The LUNA 3 trial included investigators and participants from diverse regions, reflecting the global burden of ITP and the universal need for improved therapies. Sites ranged from the United States and Europe to Asia and South America, underscoring the broad applicability of these findings. For hematologists worldwide, rilzabrutinib could offer another option for their chronic ITP patients, particularly in resource-constrained settings where frequent monitoring and hospital visits pose significant barriers to care (providing that drug costs can be overcome).
Looking Ahead
While the results of the LUNA 3 trial are promising, several questions remain. Longer-term data on sustained efficacy, safety, and QoL improvements will be critical to fully assessing rilzabrutinib’s role in the treatment algorithm. Additionally, studies exploring its use in pediatric populations and in combination with other therapies could unlock further potential.
In a field hungry for innovation, rilzabrutinib offers a beacon of hope — proof that targeted therapies can deliver meaningful, life-changing benefits to patients. Stay tuned as the data unfolds and the future of ITP management takes shape.
