FDA Drug Approvals: Oncology and Hematology — Year in Review 2018

Mary L Windle, PharmD


January 15, 2019

New Drugs for Leukemia or Lymphoma

Copiktra (duvelisib)

Duvelisib is a selective oral small molecule inhibitor of phosphoinositide 3-kinase (PI3K)–gamma and PI3K-delta isoforms expressed in normal and malignant B cells. It is indicated for relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or follicular lymphoma.

Approval was based in part on the phase 3 DUO clinical trial (n=319). Patients with relapsed/refractory CLL/SLL were randomized 1:1 to receive duvelisib 25 mg twice daily or ofatumumab 300 mg on day one, followed by 7 weekly infusions and 4 monthly infusions of 2000 mg. Duvelisib reduced the risk of disease progression or death by 48% compared with ofatumumab, and more patients responded to duvelisib compared with ofatumumab (73.8% vs 45.3%; P <.0001 for both CLL and SLL). The median progression-free survival was longer among those treated with duvelisib (13.3 vs 9.9 months; P <.0001), including in patients with del17p mutation (12.7 vs 9 months; P=.0011). Overall survival was similar between the two treatment cohorts (P=.48). (Blood. 2018 Oct 4. pii: blood-2018-05-850461)

Lumoxiti (moxetumomab pasudotox)

Moxetumomab pasudotox is an anti-CD22 recombinant immunotoxin indicated patients with for relapsed or refractory hairy cell leukemia who have received at least two prior systemic therapies, including a purine nucleoside analog. Approval was based on efficacy and safety data from a single-arm, open-label clinical trial (n=372). The phase 3 trial results showed the durable complete response (CR) rate was 30%, the CR rate was 41%, and the objective response rate (CR and partial response) was 75%. In addition, 80% achieved hematologic remission. (Leukemia. 2018 Aug;32(8):1768-1777)

Poteligeo (mogamulizumab)

Mogamulizumab is indicated for adults with two rare types of non-Hodgkin lymphoma, relapsed or refractory mycosis fungoides or Sézary syndrome, after at least one prior systemic therapy. It is a CC chemokine receptor 4 (CCR4)–directed monoclonal antibody. In patients with mycosis fungoides, cytokines released by keratinocytes promote the proclivity of the cutaneous T cells on the skin, which infuses the dermis, coats the luminal surface of the dermal endothelial cells, and up-regulates adhesion molecules in the dermal capillary endothelial lumen. This action causes a reaction to CCR4 found on cutaneous T cells.

Approval of mogamulizumab was based on the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) phase 3 clinical trial that compared mogamulizumab with vorinostat. A significantly superior progression-free survival was observed with mogamulizumab (7.7 months) compared with vorinostat (3.1 months) (P <.0001). (Lancet Oncol. 2018 Sep;19(9):1192-1204)

Asparlas (calaspargase pegol)

Calaspargase pegol catalyzes conversion of L-asparagine into aspartic acid and ammonia. The pharmacological effect is thought to be based on selective killing of leukemic cells because of depletion of plasma L-asparagine. It is indicated as part of a multiagent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients aged 1 month to 21 years. Calaspargase pegol provides a longer interval between doses and has an extended shelf-life beyond that of current pegylated asparaginase products.

Approval was based on demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using a dose of 2500 U/m2 given intravenously every 3 weeks. The pharmacokinetics were studied in a cohort of 124 patients with B-cell lineage ALL who were a median age of 11.5 years (range, 1-26 years). (Medscape Medical News)

Elzonris (tagraxofusp)

Tagraxofusp, a CD123-directed cytotoxin, is indicated for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children aged 2 years or older.

Approval was based on results from a multicenter, multicohort, open-label, single-arm clinical trial of 47 patients with BPDCN. Within this cohort, 32 patients were treatment naive and 15 patients had been previously treated. Tagraxofusp was administered on days 1 to 5 of a 21-day cycle for multiple consecutive cycles. The trial was divided into three stages: stage 1 (lead-in, dose escalation), stage 2 (expansion), and stage 3 (pivotal, confirmatory). Patients were also enrolled in an additional cohort (stage 4) to enable uninterrupted access to the drug.

In the stage 3 (pivotal) cohort, 13 patients with treatment-naive BPDCN were treated, and efficacy was based on the rate of complete response or clinical complete response (CR/CRc), with CRc defined as CR with residual skin abnormality not indicative of active disease. The CR/CRc rate was 53.8% (7 of 13), and the median duration of CR/CRc was not reached (range, 3.9-12.2 months). (Stemline)


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