Dr. Awan Discusses Distinguishes Among Available BTK Inhibitors in MCL

Farrukh Awan, MD, professor, Department of Internal Medicine, UT Southwestern Medical Center, member, Division of Hematology and Oncology, Harold C. Simmons Comprehensive Cancer Center, compares the efficacy and safety of BTK inhibitors in the management of mantle cell leukemia (MCL).

After gaining approval in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), the BTK inhibitors ibrutinib (Imbruvica), zanubrutinib (Brukinsa) and acalabrutinib (Calquence) were assessed in MCL, Awan begins. Several trials have reported efficacy data on the individual use of BTK inhibitors; however, Awan states there have been limited data comparing the 3 BTK inhibitors head to head.

Preliminary toxicity data on the use of ibrutinib vs acalabrutinib vs zanubrutinib show that these agents are similarly well tolerated in MCL, which allows patients to choose from several options, Awan says.

If an agent leads to poorly tolerated adverse effects (AEs) for an individual patient, they can choose another effective therapy, he adds.

According to toxicity data, the incidence of AEs appears to have increased with ibrutinib in MCL compared with CLL, Awan notes. However, ibrutinib is often administered at a higher dose level in MCL, he explains.

Although there are no direct efficacy comparisons of these options, zanibrutinib appears nominally more effective than acalabrutinib and ibrutinib, Awan continues. Early efficacy data show that the agent has a high response rate and elicits a median progression-free survival (PFS) of 18 to 36 months, Awan details.

In addition to BTK inhibitor monotherapies the administration of BTK inhibitors in combination with standard chemotherapy is also being investigated as a first-line treatment for MCL, Awan says. Ibrutinib plus bendamustine and rituximab (Rituxan) followed by rituximab maintenance was investigated in the phase 3 SHINE trial (NCT01776840) of elderly patients with MCL. The addition of ibrutinib to this regimen significantly prolonged PFS when compared with bendamustine and rituximab alone, Awan concludes. The regimen’s safety profile was also deemed consistent with known toxicities for each individual agent.

Editor's Note: Dr. Awan reports serving as a consultant or in an advisory role for AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, Bristol-Myers Squibb, Cardinal Health, Celgene, Dava Oncology, Epizyme, Genentech, Gilead Sciences, Incyte, Janssen, Johnson & Johnson, Karyopharm, Kite Pharma, MEI Pharma, Merck, Pharmacyclics, Verastem, Caribou Biosciences, Cellecter; he received research funding from AbbVie/Pharmacyclics.