Addition of immunotherapy to chemotherapy improves survival rates of infants with leukemia
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Key takeaways:
- No clinically relevant toxic effects occurred among the 30 infants who received blinatumomab.
- Researchers reported superior 2-year DFS and OS rates with blinatumomab plus chemotherapy over chemotherapy alone.
The addition of blinatumomab to Interfant-06 chemotherapy appeared safe for infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia, according to data published in The New England Journal of Medicine.
The combination of the immunotherapy and chemotherapy also resulted in improved minimum residual disease response, as well as higher short-term DFS and OS rates, results of the prospective, multicenter phase 2 study showed.
“It was great to see that after decades without improvement in outcome despite intensifying chemotherapy, adding only one course of blinatumomab resulted in such a significant improvement in prognosis with very few side effects,” Inge M. van der Sluis, MD, PhD, pediatric oncologist and clinical pharmacologist at Princess Máxima Center for Pediatric Oncology in the Netherlands, told Healio. “Their chance of survival increased from 66% to 93%. The chance of their cancer coming back or children dying from their disease had lowered a great deal, from 51% to 18%.”
Background and methodology
Despite chemotherapy intensification, 3-year EFS rates remain below 40% for infants with KMT2A-rearranged acute lymphoblastic leukemia, a rare but aggressive disease. Most infants experience relapse during treatment, including about two-thirds within the first year and 90% within 2 years following diagnosis.
Researchers evaluated the safety and efficacy of blinatumomab (Blincyto, Amgen), a bispecific T-cell engager molecule targeting CD19, among 30 infants diagnosed with KMT2A-rearranged ALL within the first year of life.
Infants received chemotherapy in accordance with the Interfant-6 protocol plus a single postinduction cycle of the blinatumomab, dosed at 15 g m2 per day for 28 days.
Clinically relevant toxic effects, defined as any toxic effect that partially or directly resulted from blinatumomab and led to permanent discontinuation of the agent or death, served as the primary endpoint.
Researchers reported median follow-up of 26.3 months (range, 3.9 months to 48.2 months), and all patients receiving the full 28-day course of the agent.
Results
Researchers reported no toxic effects as defined in the primary endpoint.
However, 10 serious adverse events occurred: fever (n = 4), infection (n = 4), hypertension (n = 1) and vomiting (n = 1). Researchers reported the toxicity profile to be consistent with that observed among older patients.
Following blinatumomab infusion, 28 patients (93%) achieved minimum residual disease negativity (n = 16) or had low levels of minimum residual disease (n = 12).
All patients who continued chemotherapy achieved minimum residual disease negativity with further treatment.
Researchers reported a 2-year DFS rate of 81.6% (95% CI, 60.8-92) and 2-year OS rate of 93.3% (95% CI, 75.9-98.3) among infants who received blinatumomab and chemotherapy, compared with a 2-year DFS rate of 49.4% (95% CI, 42.5-56) and 2-year OS rate of 65.8% (95% CI, 58.9-71.8) among 214 historical controls who received only chemotherapy the Interfant-06 trial.
Next steps
Additional studies are planned to further evaluate the potential benefits of blinatumomab among infants, van der Sluis said.
“As a result of our small study, all babies with KMT2A-rearranged ALL will receive blinatumomab in the next treatment protocol ... although it should be noted that blinatumomab is not registered for first-line treatment in infants,” van der Sluis told Healio.
“A larger study in 160 patients implementing our findings is already planned and called Interfant-21,” she added. “This study will be open in 27 countries worldwide and recently included the first patients in the Netherlands. In this study, all patients will receive one or two courses of blinatumomab. We expect that replacing chemotherapy blocks with immunotherapy will lead to fewer side effects and a more efficacious treatment. So, all infants with KMT2A-rearranged ALL treated according to Interfant-21 will receive blinatumomab in their first-line treatment.”
For more information:
Inge van der Sluis, MD, PhD, can be reached at i.m.vandersluis@prinsesmaximacentrum.nl.
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