FDA approves Mylotarg for treatment of acute myeloid leukemia

The FDA today approved gemtuzumab ozogamicin for the treatment of adults with newly diagnosed, CD33-positive acute myeloid leukemia, according to the drug’s manufacturer.

The agency also approved gemtuzumab ozogamicin (Mylotarg, Pfizer) — a recombinant, humanized anti-CD33 antibody–drug conjugate — as the first treatment for pediatric patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment.

“The FDA approval of MYLOTARG fills a critical unmet need for many adults and children with AML, which can be fatal in a matter of months or even weeks if not treated and has a high relapse rate,” Liz Barrett, global president of Pfizer Oncology, said in a company-issued release. “Based on clinical data, real-world experience and support from the AML community, we are grateful MYLOTARG now has the potential to help a broad range of AML patients.”

An FDA advisory committee previously expressed its support 6-1 for gemtuzumab ozogamicin as part of combination therapy for certain patients with acute myeloid leukemia.

The FDA approved the product via accelerated review in May 2000 for monotherapy of elderly individuals with relapsed AML. However, Pfizer voluntarily withdrew the agent from the market in June 2010 after results of a postmarketing clinical trial showed the drug increased risk for death but conferred no additional benefit compared with other conventional therapies.

Pfizer resubmitted a biologics license application that sought approval of gemtuzumab ozogamicin in combination with daunorubicin and cytarabine for treatment of adults with treatment-naive CD33–positive AML.

The FDA’s approval included data from the ALFA-0701, AML-19 and MyloFrance-1 trials.

The multicenter, randomized, open-label phase 3 ALFA-0701 trial evaluated gemtuzumab ozogamicin in 271 patients with newly-diagnosed de novo AML.

Patients received a new, lower fractionated dose of 3 mg/m² gemtuzumab ozogamicin on days 1, 4 and 7 in combination with conventional chemotherapy (n = 135) or chemotherapy alone (n = 136).

Event-free survival served as the primary endpoint.

Patients who received gemtuzumab ozogamicin demonstrated improved EFS compared with patients who received chemotherapy alone (17.3 months vs. 9.5 months; HR = 0.56; 95% CI, 0.42-0.76).

The multicenter, randomized, open-label phase 3 AML-19 trial compared gemtuzumab ozogamicin monotherapy with best supportive care for elderly patients who could not tolerate other AML therapies.

As initial treatment, patients received 6 mg/m² gemtuzumab ozogamicin on day 1 and 3 mg/m² gemtuzumab ozogamicin on day 8. As continued treatment, patients without evidence of disease progression received 2 mg/m² gemtuzumab ozogamicin on day 1 every 4 weeks.

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Patients in the gemtuzumab ozogamicin group achieved a higher median OS than those who received best supportive care (4.9 months vs. 3.6 months; HR = 0.69; 95% CI, 0.53-0.9; P = .005).

The single-arm, open-label phase 2 MyloFrance-1 trial evaluated gemtuzumab ozogamicin in 57 adult patients in first relapse.

Patients received 3mg/m² gemtuzumab ozogamicin monotherapy on days 1, 4 and 7.

Fifteen patients achieved a complete remission (26%; 95% CI, 16-40), with a median relapse-free survival of 11.6 months.

The most common adverse events included hemorrhage, infection, fever, nausea, vomiting, constipation, headache, increased alanine transaminase, increased aspartate transaminase, rash and mucositis.

“Today is an important day for patients, their families and the entire AML community, as the approval of MYLOTARG brings forth a long-awaited treatment option that may lead to deeper, more durable remissions for patients with AML,” Jorge Cortes, MD, D. B. Lane cancer research distinguished professor for leukemia research at The University of Texas MD Anderson Cancer Center, said in the release. “After many years, we are finally seeing progress in the treatment of AML, which has renewed my hope in improving outcomes for my patients. I am pleased that I can now offer many adult and pediatric patients targeted treatment with MYLOTARG.”