Lenalidomide/Dasatinib Receive FDA Approval in Hematologic Malignancies

Lenalidomide capsules and dasatinib tablets have received FDA approval through an abbreviated new drug application for various hematologic malignancies.

The FDA has given approvals for abbreviated new drug applications (ANDAs) in lenalidomide (Revlimid) capsules, dasatinib (Sprycel) tablets in multiple hematologic indications, according to a news release from the drug’s developer, Biocon Pharma.1 Rivaroxaban (Xarelto) tablets have also received tentative approval.

Lenalidomide has been approved in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg doses for the treatment of multiple myeloma (MM), mantle cell lymphoma (MCL), follicular lymphoma, marginal zone lymphoma, and anemia in myelodysplastic syndromes (MDS) in adult patients.

Dasatinib has been approved in 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, and 140 mg doses to treat Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in children 1 year and older as well as adults, pretreated adults with Ph+ CML or acute lymphoblastic leukemia (ALL), and children 1 year and older with newly diagnosed Ph+ ALL in combination with chemotherapy.

Rivaroxaban can be given in 2.5 mg, 10 mg, 15 mg, and 20 mg doses to treat patients with deep vein thrombosis and pulmonary embolism.

Based on the package insert, notable warnings and precautions for lenalidomide use include allergic reactions, tumor lysis syndrome (TLS), tumor flare reactions, hepatotoxicity, and second primary malignancies.2 Lenalidomide was additionally found to cause embryo-fetal toxicity during pregnancy in a developmental monkey study similar to birth defects caused by thalidomide (Thalomid). Additionally, for patients with del 5q myelodysplastic syndromes, lenalidomide may cause neutropenia and thrombocytopenia. In patients receiving lenalidomide with dexamethasone for multiple myeloma, an increased risk of deep vein thrombosis and pulmonary embolism was observed.

Common adverse effects (AEs) occurring in 20% or more of patients undergoing lenalidomide treatment for multiple myeloma include fatigue, neutropenia, constipation, diarrhea, muscle cramps, anemia, pyrexia, peripheral edema, nausea, back pain, upper respiratory tract infection, dyspnea, dizziness, thrombocytopenia, tremor, and rash. AEs occurring in 15% or more of patients undergoing lenalidomide treatment for myelodysplastic syndrome include thrombocytopenia, neutropenia, diarrhea, pruritus, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, pharyngitis, and epistaxis. Furthermore, AEs occurring in 15% or more of patients undergoing lenalidomide treatment for MCL include neutropenia, thrombocytopenia, fatigue, diarrhea, anemia, nausea, cough, pyrexia, rash, dyspnea, pruritus, constipation, peripheral edema, and leukopenia.

In patients also taking digoxin (Lanoxin), monitoring of plasma levels is recommended due to increased maximum plasma concentration (C­­­­­­max) and area under the curve (AUC) with concomitant lenalidomide. Additionally, an increased risk of venous thromboembolism was observed with concomitant erythropoietin stimulating agents or estrogen containing therapies. Nursing mothers should either discontinue therapy or nursing, and patients with renal insufficiency should adjust the starting dose of lenalidomide.

Notable warnings and precautions for dasatinib use include myelosuppression, bleeding related events, fluid retention, QT prolongation, congestive heart failure, and fetal harm when administered to a pregnant individual.3

AEs occurring in 10% or more of patients taking dasatinib for newly diagnosed chronic phase CML include myelosuppression, fluid retention, diarrhea, headache, musculoskeletal pain, and rash. Additionally, AEs occurring in 20% or more of patients with resistance or intolerance to prior imatinib (Gleevec) therapy include myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage.

In patients taking CYP3A4 inhibitors and inducers, treatment with dasatinib is not recommended due to drug level increases and decreases, respectively. If coadministration cannot be avoided, dose reductions and increases in respective indications, as well as monitoring, should be employed. Antacids and H2 antagonists or proton pump inhibitors may decrease dasatinib drug levels, with antacids recommended in place of H2 antagonists or proton pump inhibitors. Antacids should be given at least 2 hours before or after dasatinib dosing.

References

1. Biocon Pharma Limited secures U.S. FDA approvals for lenalidomide and dasatinib. Biocon Pharma. March 4, 2025. Accessed March 5, 2025. https://tinyurl.com/4ep82mru
2. REVLIMID [lenalidomide] capsules, for oral use. Prescribing information. FDA, 2013. Accessed March 6, 2025. https://tinyurl.com/4e2k49ny
3. SPRYCEL® (dasatinib) tablet for oral use. Prescribing information. FDA, 2010. Accessed March 6, 2025. https://tinyurl.com/hyjx4rz5