New ALL option advances

Administration of antibody-based drug inotuzumab ozogamicin led to impressive remission rates, qualified ALL patients for curative stem cell transplant in Phase 3 study

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HOUSTON—Acute lymphoblastic leukemia, or acute lymphocytic leukemia (ALL), begins in the lymphocytes in the bone marrow. Leukemias can invade the blood and metastasize particularly quickly, which makes for generally poor prognoses for this cancer type. B-cell ALL begins in B cells, or B lymphocytes, which “protect the body from invading germs by maturing into plasma cells, which makes proteins called antibodies,” the American Cancer Society explains.
Current statistics for patients with ALL aren't encouraging. According to the American Cancer Society, there will be approximately 6,500 new cases of ALL this year, with a forecasted 1,430 deaths from this cancer. Complete remission rates for existing therapies for adults with newly diagnosed B-cell ALL are between 60 to 90 percent, but many with complete remission relapse, and only about 30 to 50 percent have disease-free survival of three years or more. The current chemotherapy regimens for adults with relapsed or refractory B-cell ALL generally produce rates of complete remission of 31 to 44 percent when administered after an early relapse. The only potentially curative treatment option for ALL is allogeneic stem cell transplantation, which generally has a prerequisite of complete remission.
However, a multi-institution study of an antibody-drug conjugate might offer a new treatment option for ALL patients that could help them reach remission and qualify for transplantation.
The drug in question is Pfizer Inc.'s inotuzumab ozogamicin, or CMC-544. The compound links an antibody that targets the protein CD22, which is found on the surface of more than 90 percent of ALL cells. Once the drug links to CD22, the ALL cell draws it inside and dies.
“Forty-one percent of ALL patients in the study were able to proceed to transplant after receiving inotuzumab ozogamicin compared with the 11 percent we have seen qualify through standard chemotherapy,” Dr. Hagop Kantarjian, chair of Leukemia, said in a press release. “Given that stem cell transplant is considered the only curative treatment option, the ability of inotuzumab ozogamicin to increase the number of patients able to bridge to transplant is encouraging.”
“Standard chemotherapy regimens result in complete remission in 31 to 41 percent of patients who relapse earlier, and just 18 to 25 percent in those who relapse later,” Kantarjian added. “Patients in the inotuzumab ozogamicin study had remission rates of 58 percent, higher than previously reported, possibly due to patients being treated later in the disease course.”
In a randomized Phase 3 study of inotuzumab ozogamicin, a statistically significant percentage of patients with ALL whose disease had relapsed following standard therapies qualified for stem cell transplants. Participants saw complete remission rates of almost 81 percent, as well as significantly longer progression-free and higher overall survival rates than with standard therapies. The study was conducted at The University of Texas MD Anderson Cancer Center, with funding provided by Pfizer, and the findings were published online in the New England Journal of Medicine.
“Adult patients with relapsed or refractory ALL have a five-year survival rate of less than 10 percent, making these patients particularly difficult to treat. To see remission rates and two-year survival rates that are more than doubled compared to standard of care chemotherapy is very gratifying. We believe these data add to the growing body of evidence that supports inotuzumab ozogamicin as an important potential treatment option in adults with relapsed or refractory ALL,” Dr. Mace Rothenberg, chief development officer, Oncology, Pfizer Global Product Development, said regarding the study results.
Patients treated with inotuzumab ozogamicin did see moderate side effects, the most common being cytopenia, a disorder that reduces blood cell production, and liver toxicity.
Other participating institutions for this work included Dana-Farber Cancer Institute; Universitätsklinikum Münster; University of Bologna; Stanford Cancer Institute; University of Chicago; Goethe University; University of California, Irvine; Pfizer; and Cleveland Clinic.

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