Recent FDA Approvals

Best Practices in Hematologic Malignancies – December 2017 Vol 8

Calquence Approved for Mantle Cell Lymphoma

On October 31, 2017, the FDA granted accelerated approval to acalabrutinib (Calquence) for the treatment of adults with mantle cell lymphoma (MCL) who have received at least 1 previous therapy. The FDA granted acalabrutinib priority review, breakthrough therapy, and orphan drug designation for this indication.

The safety and efficacy of acalabrutinib were evaluated in study LY-004, an open-label, phase 2 clinical trial involving 124 patients with MCL who received at least 1 previous therapy. Acalabrutinib 100 mg twice daily was administered orally until disease progression or unacceptable toxicity. The primary efficacy end point was overall response rate (ORR), and the median follow-up was 15.2 months. The investigator-assessed ORR was 81% (95% CI, 73%-87%), and the median duration of response was not reached.

The most common adverse reactions reported with acalabrutinib include anemia, thrombocytopenia, headache, neutropenia, diarrhea, fatigue, myalgia, and bruising.

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Yescarta CAR T-Cell Therapy Approved for Large B-Cell Lymphoma

On October 18, 2017, the FDA approved axicabtagene ciloleucel (Yescarta), a CD19-directed genetically modified autologous T-cell immunotherapy, for the treatment of adults with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The FDA granted Yescarta priority review, breakthrough therapy designation, and orphan drug designation for this indication.

“The approval of Yescarta brings this innovative class of CAR T-cell therapies to an additional group of cancer patients with few other options–those adults with certain types of lymphoma who have not responded to previous treatments,” said Peter Marks, MD, PhD, Director, FDA’s Center for Biologics Evaluation and Research.

The safety and efficacy of axicabtagene ciloleucel were evaluated in a single-arm, open-label, multicenter trial involving 111 adults with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. The primary efficacy end points were complete remission rate and duration of response, as determined by an independent review committee. Of the 101 evaluable patients who received axicabtagene ciloleucel, 51% achieved a complete remission, and 21% achieved a partial remission. The median time to response was 0.9 months (range, 0.8-6.2 months), and the median duration of response was 9.2 months.

The most common (20%) adverse reactions reported with axicabtagene ciloleucel are cytokine release syndrome, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections (pathogen unspecified), nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

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Aliqopa Approved for Adults with Relapsed Follicular Lymphoma

The FDA granted accelerated approval on September 14, 2017, to copanlisib (Aliqopa) for the treatment of adults with relapsed follicular lymphoma who have received at least 2 previous systemic therapies. Copanlisib received priority review and orphan drug designation for this indication.

“For patients with relapsed follicular lymphoma, the cancer often comes back even after multiple treatments,” said Richard Pazdur, MD, Acting Director, FDA’s Office of Hematology and Oncology Products, and Director, FDA’s Oncology Center of Excellence. “Options are limited for these patients, and today’s approval provides an additional choice for treatment, filling an unmet need for them,” he added.

The approval of copanlisib for patients with relapsed follicular lymphoma was based on the single-arm, multicenter, phase 2 clinical trial CHRONOS-1 involving 104 patients with follicular B-cell non-Hodgkin lymphoma that relapsed after at least 2 previous therapies. The primary efficacy end point was overall response rate (ORR). ORR was 59% (95% CI, 49%-68%), median duration of response was 12.2 months, and median time to response was 1.7 months (range, 1.3-9.7 months).

The most common (≥20%) adverse reactions reported with copanlisib therapy include hyperglycemia, diarrhea, decreased general strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory tract infections, and thrombocytopenia.

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Actemra First FDA-Approved Treatment for CAR T-Cell–Induced Severe Cytokine Release Syndrome

In association with the approval of the first chimeric antigen receptor (CAR) T-cell therapy, on August 30, 2017, the FDA also accelerated the approval of a new indication as an orphan drug for tocilizumab (Actemra), a humanized interleukin-6 receptor antagonist, for the treatment of patients aged ≥2 years with CAR T-cell–induced severe or life-threatening cytokine release syndrome (CRS).

This new indication for tocilizumab was based on a retrospective analysis of data from clinical trials evaluating the efficacy of the drug in 45 adult and pediatric patients who received tocilizumab with or without high-dose corticosteroids for the treatment of severe or life-threatening CRS. Overall, 31 patients (69%) achieved a response, which was defined as the resolution of CRS within 14 days of the first tocilizumab dose. No more than 2 doses of tocilizumab per patient were used in the trial. No tocilizumab-related adverse events were reported in the study. The results from a second trial in 15 patients with CAR T-cell–induced CRS were used to confirm the resolution of CRS within 14 days of tocil­izumab therapy.

The common side effects associated with tocilizumab include upper respiratory tract infections, headache, hypertension, and injection-site reactions. Serious side effects include an increased risk for serious infections and certain cancer types, tears in the stomach, thrombocytopenia, neutropenia, hepatitis B infection, serious allergic reactions, and central nervous system problems.

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Blincyto Receives Expanded Indication to Include Patients with Ph+ B-Cell Precursor ALL

On July 11, 2017, the FDA approved an expanded indication for blinatumomab (Blincyto) to include the treatment of patients with Philadelphia chromosome (Ph)-positive (Ph+), relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

This current regular FDA approval also provides confirmation of the 2014 accelerated approval granted to blinatumomab for the treatment of patients with Ph-negative relapsed or refractory B-cell precursor ALL. It also expands the indication to include all patients with relapsed or refractory B-cell precursor ALL, regardless of their Ph chromosome status.

The study that confirmed the initial approval was based on TOWER, a randomized clinical trial that compared blinatumomab and standard-of-care chemotherapy in 405 patients with relapsed or refractory B-cell precursor ALL. Results showed significant improvement in overall survival (OS) with blinatumomab versus chemotherapy (hazard ratio, 0.71; P = .012); the estimated median OS was 7.7 months versus 4.0 months, respectively.

The expanded indication to patients with Ph+ disease was based on ALCANTARA, a single-arm multicenter study of 45 patients with Ph+ relapsed or refractory B-cell precursor ALL. Overall, 36% of patients reached complete remission with blinatumomab, with a median remission duration of 6.7 months.

The 2 studies did not report any new major adverse events.

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First FDA-Approved Test to Help Detect Several Leukemias and Lymphomas

On June 29, 2017, the FDA authorized the marketing of ClearLLab Reagents, the first test that is agency approved to aid flow cytometry in the marking and detecting of several blood cancers, including chronic leukemia, acute leukemia, non-Hodgkin lymphoma, myeloma, myelodysplastic syndrome, and myeloproliferative neoplasms.

The ClearLLab test, which uses a fluorescent dye to mark proteins on the surface of cells for further analysis with a flow cytometer, identifies cancerous cells in blood, bone marrow, and lymph nodes, and gives clinicians information about the type of leukemia or lymphoma that is present.

“This represents a major step forward for the hematology-oncology community. Laboratories and healthcare professionals now have access to an FDA-validated test that provides consistent results to aid in the diagnoses of these serious cancers,” said Alberto Gutierrez, PhD, Director of the FDA Center for Devices and Radiological Health. The ClearLLab test approval was based on a study showing that the ClearLLab test accurately detected the presence of cancer 84.2% of the time.

The FDA notes that ClearLLab Reagents test results must be reviewed by trained professionals.

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Rituximab Combination Now Approved in 3 Blood Cancers

On June 22, 2017, the FDA approved the combination of rituximab and hyaluronidase human (Rituxan Hycela) for the treatment of adults with follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), or chronic lymphocytic leukemia (CLL).

Specifically, this approval covers indications that were previously approved for rituximab alone, including patients with previously untreated or nonprogressing relapsed or refractory follicular lymphoma, previously untreated DLBCL, and previously treated and untreated CLL.

This approval gives patients a subcutaneous route for receiving rituximab that shortens its administration time to 5 to 7 minutes (compared with the several hours that an intravenous infusion can take) and provides the option of flat dosing.

The FDA’s approval was based on multiple randomized clinical trials that demonstrated the noninferiority of rituximab trough concentration levels in the combination therapy to those of intravenous rituximab, as well as the comparable efficacy and safety of the combination therapy and rituximab monotherapy.

In patients with follicular lymphoma, the most common (≥20%) adverse events associated with the combination therapy include infections, neutropenia, nausea, constipation, cough, and fatigue. For patients with DLBCL, the most common (≥20%) adverse events include infections, neutropenia, alopecia, nausea, and anemia. In patients with CLL, the most common (≥20%) adverse events are infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection-site erythema.

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Welcome to the Fourth Annual Oncology Guide to New FDA Approvals
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The Lynx Group is pleased to bring you the Fourth Annual Oncology Guide to New FDA Approvals. The goal of this Guide is to offer oncologists, pharmacists, oncology nurses, and other healthcare stakeholders a comprehensive overview of new drugs approved by the US Food and Drug administration (FDA) in 2018 for the treatment of different types of cancer, including hematologic and oncologic malignancies. This practical tool offers a quick, evidence-based resource for hematology/oncology professionals to guide their medication-related decision-making and help ensure the administration of recent medicines for appropriate patients.
Last modified: June 9, 2018

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