New Drugs for Hematologic Malignancies

Kristen Coppock, MA, Managing Editor

Directions in Pharmacy, February 2021, Volume 3, Issue 1

Presentation provides an overview of recent FDA approvals for therapies utilized in patients with various cancer types.

Several oncology drugs have been approved by the FDA since 2019 for treating hematologic malignancies. Heidi D. Finnes, PharmD, BCOP, FHOPA, highlighted some of these approved therapies during the Advanced Practitioner Society for Hematology and Oncology annual meeting, 2020 JADPRO Live Virtual.1

Finnes, a senior manager of pharmacy cancer research at Mayo Clinic in Rochester, Minnesota, provided clinical study data for each drug she presented, as well as other information pertinent to oncology pharmacists, such as adverse effects (AEs). The highlighted drugs are indicated for various hematologic cancer types. The overview included the following drugs.

Zanubrutinib (Brukinsa; BeiGene)

A Bruton tyrosine kinase (BTK) inhibitor, zanubrutinib was approved in November 2019 for treatment of mantle cell lymphoma (MCL) after a minimum of 1 prior therapy. Taken orally—320 mg/day or 160 mg twice daily—this drug achieved an 84% overall response rate (ORR), with 69% of patients achieving an objective response and 15% partial ORR in the phase 2 BGB-3111-206 study (NCT03206970).1

“The primary end point of this trial was ORR,” Finnes said. “Eighty-six patients were enrolled, and most had received at least 2 lines of therapy.”

In this study, time to response was 2.7 months, median duration of response was 19.5 months, and median progression-free survival (PFS) was 22.1 months.

Zanubrutinib has possible serious AEs, including bleeding problems, infections, decreases in blood cell counts, second primary cancers that may include skin malignancies, heart rhythm problems such as atrial fibrillation, and embryo-fetal toxicity.1,2

According to investigators, BCG-3111- 206 study results demonstrate zanubrutinib as generally well tolerated.3 AEs occurring in 20% or more of patients taking zanubrutinib included neutropenia, thrombocytopenia, anemia, upper respiratory tract infection, rash, diarrhea, bruising, and cough.2 Grade 3 or greater BTK inhibitor toxicities were uncommon.3

According to Finnes, zanubrutinib may be utilized in patients with relapsed/refractory MCL, particularly those with TP53-mutated tumors, as well as those who may be concerned about BTK inhibitor toxicity.1

According to data cited by Finnes, zanubrutinib costs $15,522 for an average 30-day cycle.1

Tafasitamab-cxix (Monjuvi; MorphoSys US)

An anti-CD19 monoclonal antibody, tafasitamabcxix was approved in July 2020 for adult patients with relapsed/refractory transplant-ineligible diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide (Revlimid; Bristol Myers Squibb). Its formulation is 200-mg lyophilized powder.1

According to Finnes, intravenous (IV) tafasitamabcxix is given after premedication at a dose of 12 mg/kg on cycle 1, on days 1, 4, 8, 15, and 22; during cycles 2 and 3, weekly on days 1, 8, 15, and 22; and cycles 4 and above on days 1 and 15 of a 28-day cycle.1

“Of note, lenalidomide is given for a maximum of 12 cycles,” said Finnes.1

The FDA recommends dosing with tafasitamab-cxix at 12 mg/kg as an IV infusion.4

Efficacy of tafasitamab-cxix with lenalidomide was evaluated in the open-label, multicenter singlearm trial L-MIND (NCT02399085) that enrolled 81 patients. These patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles. Patients followed these cycles with tafasitamab-cxix as monotherapy.4

Efficacy of tafasitamab-cxix was based on best ORR. In 71 patients with a diagnosis of DLBCL, best ORR was 55% (95% CI, 43%-67%), with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months.4

Serious AE warnings for tafasitamab-cxix include infusion-related reactions, myelosuppression, infections, and embryo-fetal toxicity.5

“It would be important to monitor patients for signs and symptoms of infection and potentially consider white blood cell colony-stimulating factors, if needed,” Finnes said.

The most common AEs (≥ 20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.4,5

According to Finnes, tafasitamab-cxix costs $7200 per dose for a patient weighing 83 kg, or about 183 pounds.1

Isatuximab-irfc (Sarclisa; Sanofi)

An anti-CD38 monoclonal antibody, isatuximab-irfc was approved by the FDA in March 2020 for patients with relapsed/refractory multiple myeloma with 2 prior therapies. Its formulation consists of a 100-mg/5 mL and 500-mg/25 mL solution.1

Recommended dosing for isatuximab-irfc is 100 mg/ kg as an IV infusion every week for 4 weeks, followed by every 2 weeks in combination with pomalidomide (Pomalyst; Bristol Myers Squibb) and dexamethasone (DexPak; Bausch Health) until disease progression or unacceptable toxicity.1,6

Approval of isatuximab-irfc was based on the results of the phase 3 ICARIA-MM (NCT02990338) trial, according to Finnes.1 Of the 307 enrolled patients in this trial, 154 were randomized to receive isatuximab-irfc with pomalidomide and low-dose dexamethasone (Isa-Pd), and 153 patients were randomized to receive pomalidomide and low-dose dexamethasone (Pd).7

“Significantly more patients in the Isa-Pd group achieved a partial response or a very good partial response. The median time to response was shorter in the Isa-Pd group, and the duration of response was longer. Overall survival at 12 months was 72% in the Isa-Pd arm and 63% in the Pd arm,” Finnes said.1

The main measure of efficacy was PFS, which was assessed using International Myeloma Working Group criteria. The improvement in PFS represented a 40% reduction in the risk of disease progression or death in patients treated with Isa-Pd (HR, 0.596; 95% CI, 0.44-0.81; P = .0010). Median PFS for patients who received Isa-Pd was 11.53 months (95% CI, 8.94- 13.9), compared to 6.47 months (95% CI, 4.47-8.28) among those patients in the Pd arm.7

Label warnings for isatuximab-irfc include infusion-related reactions, neutropenia, second primary malignancies, laboratory test interference, and embryo-fetal toxicity. The most common AEs associated with isatuximab-irfc, occurring in 20% or more of patients, were neutropenia, anemia, thrombocytopenia, lymphopenia, infusion-related reactions, pneumonia, upper respiratory tract infection, and diarrhea.1,7

The cost of isatuximab-irfc is $6240 per dose for a patient weighing 80 kg, or about 176 pounds, according to Finnes.1

In addition to zanubrutinib, tafasitamab-cxix, and isatuximab-irfc, Finnes included in her presentation additional drugs recently approved by the FDA for hematologic malignancies.1

REFERENCES

  • Finnes HD. New drug updates in hematologic malignancies. Presented at: 2020 JADPRO Live Virtual; October 15-23, 2020; online.
  • Brukinsa. Prescribing information. BeiGene; 2019 . https://www.brukinsa.com/prescribing-information.pdf
  • Song Y, Zhou K, Zou D, et al. Treatment of patients with relapsed or refractory mantle-cell lymphoma with zanubrutinib, a selective inhibitor of Bruton’s tyrosine kinase. Clin Cancer Res. 2020;26(16):4216-4224. doi: 10.1158/1078-0432.CCR-19-3703
  • FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. August 3, 2020. Accessed November 18, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tafasitamab-cxix-diffuse-large-b-cell-lymphoma
  • Monjuvi. Prescribing information. MorphoSys USA; 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761163s000lbl.pdf
  • Sarclisa. Prescribing information. Sanofi; 2020. http://products.sanofi.us/Sarclisa/sarclisa.pdf
  • FDA approves isatuximab-lrfc for multiple myeloma. FDA. March 2, 2020. Accessed November 20, 2020. https://www.fda.gov/drugs/development-approval-process-drugs/fda-approves-isatuximab-irfc-multiple-myeloma