Expert Highlights Advances Across Lymphoma Subtypes

The preferred regimen for patients with advanced stage Hodgkin lymphoma remains a question debated among physicians who treat this patient population, said Alison J. Moskowitz, MD.

One of the most important prognostic factors of how a patient will respond to therapy is a PET scan after receiving doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD). Interim PET-CT scanning was successfully used to adapt treatment regimens in patients with advanced classical Hodgkin lymphoma, according to the results of the international RATHL trial. Although the results fell short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen resulted in a lower incidence of pulmonary toxic events versus continued treatment with ABVD but not in significantly lowered efficacy.

With a median follow up of 41 months, the 3-year progression-free survival (PFS) rate and overall survival rate in the ABVD group was 85.7% (95% CI, 80.7%-87.5%) and 97.6% (95% CI, 95.1%-98.7%), respectively, versus 84.4% (95% CI, 80.7-87.5) and 97.6% (95% CI, 95.6-98.7) in the doxorubicin, vinblastine, and dacarbazine (AVD) arm.¹

“This trial is showing that a PET scan after ABVD is predictive of how a patient is doing. A patient with a PET2-negative scan has a 90% to 95% chance of being cured. That chance is much lower for a patient who is PET2-positive. Based upon these data, there have been efforts to use PET scan to both escalate and de-escalate treatment to modify it to what the patient needs,” said Moskowitz.

Additionally, brentuximab vedotin was FDA approved in March 2018 as a frontline treatment for patients with Hodgkin lymphoma based on the results of the phase III ECHELON-1 trial. This study demonstrated superior PFS with brentuximab vedotin plus AVD compared with ABVD. Brentuximab vedotin reduced the risk of progression, death, or initiation of a new therapy by 23% compared with ABVD.² The 2-year modified PFS rate was 82.1% with brentuximab vedotin compared with 77.25% for ABVD (HR, 0.77; 95% CI, 0.60-0.98; P = .035).

Brentuximab vedotin has been investigated across additional diseases beyond Hodgkin lymphoma. The phase III ALCANZA trial led to the November 2017 FDA approval of brentuximab vedotin for the treatment of patients with cutaneous T-cell lymphoma (CTCL). In this trial, the objective responses lasting more than 4 months were 56.3% in patients treated with brentuximab vedotin compared with 12.5% in patients receiving physician’s choice of standard therapies (P <.0001). At a median follow-up of 17.5 months, the median PFS was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice (HR, 0.270; 95% CI, 0.169-0.430; P <.0001). The objective response rate (ORR) was 67% versus 20% with complete response rates of 16% versus 2%, respectively.³

“There was a group that benefited from treatment with brentuximab vedotin, which is what I observed in my own practice. Patients who have a large burden of disease or tumor-based disease often have brisk responses of treatment in those areas,” explained Moskowitz.

A regimen that is not yet approved for the treatment of patients with CTCL is mogamulizumab. The use of mogamulizumab was found to reduce the risk of progression or death by 47% compared with vorinostat (Zolinza) in patients with previously treated CTCL, according to the phase III MAVORIC study. The FDA granted a priority review to a biologics license application for mogamulizumab for this patient population based on these findings.

MAVORIC included 372 patients with historically confirmed stage IB to IVB mycosis fungoides or Sézary syndrome (2 subtypes of CTCL) who had failed more than 1 prior line of therapy. The investigator-assessed median PFS was 7.7 months (95% CI, 5.7-10.3) in the mogamulizumab arm compared with 3.1 months (95% CI, 2.9-4.1) in the vorinostat arm (HR, 0.53; 95% CI, 0.41-0.69; P <.0001). The ORR was 28% with mogamulizumab versus 4.8% with vorinostat (P <.0001).⁴

According to Moskowitz, when comparing brentuximab vedotin and mogamulizumab for patients with CTCL, there are several differences, such as the eligibility criteria and toxicity limits. For brentuximab vedotin, patients tend to have brisk responses with large cell transformation tumor-based disease, which is a different patient population than those who respond to mogamulizumab. A downside of brentuximab vedotin is that patients eventually develop neuropathy, which is a bigger issue in CTCL than in Hodgkin lymphoma. Physicians aim for chronic disease control in patients with CTCL, which is when mogamulizumab comes into play.

“These differences help physicians determine which is the best treatment for their individual patients,” said Moskowitz.

References

1. Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016;374(25):2719-2429. doi: 10.1056/NEJMoa1510093.
2. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine (A+AVD) as frontline therapy demonstrates superior modified progression-free survival versus ABVD in patients with previously untreated stage III or IV Hodgkin lymphoma (HL): the phase 3 ECHELON-1 study. In: Proceedings from the 59th Annual ASH Meeting and Exposition; December 9-12, 2017; Atlanta, Georgia. Abstract 6.
3. Kim YH, Whittaker S, Horwitz SM, et al. Brentuximab vedotin demonstrates significantly superior clinical outcomes in patients with CD30-expressing cutaneous T cell lymphoma versus physician’s choice (methotrexate or bexarotene): the phase 3 ALCANZA study. In: Proceedings from the 58th Annual ASH Meeting and Exposition; December 3-6, 2016; San Diego, California. Abstract 182.
4. Kim YH, Bagot M, Pinter-Brown , et al. Anti-CCR4 monoclonal antibody, mogamulizumab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL): results from the phase III MAVORIC study. In: Proceedings from the 59th Annual ASH Meeting and Exposition; December 9-12, 2017; Atlanta, Georgia. Abstract 817.

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“We now have brentuximab vedotin (Adcetris) approved in the frontline setting for Hodgkin lymphoma, which brings up the question on everyone’s mind of what the preferred regimen for patients with advanced-stage Hodgkin lymphoma is,” Moskowitz said in a presentation at the 2018 OncLive^® State of the Science Summit™ on Hematologic Malignancies. Moskowitz is clinical director of the Lymphoma Inpatient Unit at Memorial Sloan Kettering Cancer Center.