Conference Coverage

Cerdulatinib yields ‘encouraging’ results in CTCL, PTCL

Key clinical point: Cerdulatinib produced responses in patients with relapsed or refractory T-cell lymphomas.

Major finding: The overall response rate was 34% in patients with peripheral T-cell lymphoma (PTCL) and 26% in patients with cutaneous T-cell lymphoma (CTCL).

Study details: Expansion cohorts of a phase 2 trial including 45 PTCL patients and 29 CTCL patients

Disclosures: The study was funded by Portola Pharmaceuticals. The investigator reported having no relevant conflicts.


 

REPORTING FROM TCLF 2019

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.

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In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.

Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

  • 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
  • 2 CRs in PTCL not otherwise specified.
  • 1 CR in gamma-delta T-cell lymphoma.
  • 1 PR in ALK-negative anaplastic large-cell lymphoma.
  • 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

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