Optimizing Brentuximab Vedotin Use in Hodgkin Lymphoma

Leo Gordon, MD:We’re especially concerned about the neurotoxicity of brentuximab vedotin because we’re giving it together with Velban [vinblastine], which we know is a potentially neurotoxic agent that can cause peripheral neuropathy, constipation, and muscle cramping. And so, the combination of those 2 is something that is of some concern, and the addition of brentuximab to the entire treatment regimen results in greater neutropenia.

What are alternatives to this? Well, I mentioned that the ECHELON study was recently published, but more recently even—I would say about 3 weeks ago—we published data from a cooperative study between our institution and a number of other institutions around the country. We did the study with MD Anderson, Memorial Sloan Kettering, Stanford, and several other institutions looking at a population of older patients. In this study, patients had to be older than 60, but I think some patients over the age of 55 were included. This tested the use of brentuximab vedotin, but as a lead-in for 3 cycles, just by itself, followed by AVD [doxorubicin/vinblastine/dacarbazine] chemotherapy.

We were not giving brentuximab together with Adriamycin [doxorubicin], Velban, and DTIC [dacarbazine]. After the end of 4 to 6 cycles of AVD, we gave a consolidation of brentuximab for 3 or 4 cycles. The data were just published in theJournal of Clinical Oncologythis past month and suggest the best outcomes in patients over the age of 60 that are available in the literature today. The toxicity was fairly manageable, especially in patients who didn’t have a lot of comorbidities, which is always a concern in older patients.

We were able to mitigate some of the toxicities of brentuximab vedotin when given together with AVD by separating them, using the lead-in brentuximab and then going to AVD. We didn’t see severe neutropenia, nor did we see the severe peripheral neuropathy that you see when you give those agents together. I would say that 1 alternative for patients, now that this regimen has been published, would be to use brentuximab as a lead-in and then give a AVD rather than giving them together.

This patient went on and had standard evaluation. She had a PET [positron emission tomography] scan following the second cycle of treatment and was reported as having a Deauville 2 score. We use the Deauville score to evaluate PET scans because it’s a fairly subjective evaluation, and no one has come together with a good standard of approach that can be applied across multiple institutions and multiple practices, especially places where people aren’t seeing that many cases of [Hodgkin] lymphoma.

This patient had an excellent response. We consider a Deauville 2 to be a complete remission. Some people consider a Deauville 3 to even be complete remission, but Deauville 2 certainly is completely remission. Based on data published many years ago, we know that those patients who achieve a Deauville 2 score or complete remission after 2 cycles of chemotherapy have a much better outcome than those who do not. We know early on that this patient is likely to have a relatively good outcome.

Transcript edited for clarity.

A 52-Year-Old Woman With Stage IIIa Hodgkin's Lymphoma

• History and physical exam
  • A 52-year-old female presented with abdominal pain
  • Labs: B12 deficiency, albumin 3.5 mg/dL, Hgb 11.5 g/dL, white cell and lymphocyte counts WNL
  • No B symptoms
• Right cervical excisional biopsy: classical Hodgkin’s disease, nodular sclerosis, stage IIIa
• Cardiac and lung function were normal
• IPS 2
• AVD + brentuximab (1.2 mg/kg) q2w x 6 cycles was initiated 2.5 months later

Treatment Course

Cycle 1, d 1

Leg cramping; hospitalized for neutropenic fever (d 7-14)

Cycle 1, d 15

Bone pain; constipation

Cycle 2, d 1

AVD + brentuximab delayed 1 wk due to neutropenia hospitalization; elongated QT interval (drug related); PPI initiated for reflux; constipation causing abdominal pain; numbness in hands

Cycle 2, d 5

GERD, constipation, and neuropathy unchanged

Cycle 2, d 16

Hospitalized 8 days for neutropenic fever; discharged on amoxicillin (infection source unknown)

Interim PET-CT

Complete response (Deauville score 2)

Cycle 3, d 1

Filgrastim 5 mgc/kg qd, d 5-10; treatment well tolerated; ED for bronchitis (azithromycin), good response

Cycle 3, d 15

Treatment well tolerated; ANC > 3 throughout treatment; grade 1 neuropathy (numbness in fingertips, palms, and toes)

Cycle 4, d 1

Treatment tolerated well; no fever; grade 1 neuropathy

Cycle 4, d 15

Brentuximab dose reduced to 0.8 mg/kg, due to grade 2 peripheral sensory neuropathy; transient grade 1 skin and mucosal abnormalities around day 8

Cycle 5, d 1

Grade 2 neuropathy; pregabalin for muscle pain and weakness initiated

Cycle 5, d 15

EF < 50%; slightly worsened neuropathy (impacting work and daily life); doxorubicin held (in consult with cardiologist)

Cycle 6, d 1

Doxorubicin restarted (per cardiologist/> 50% EF); grade 3 neuropathy; leg weakness increased; brentuximab held

Cycle 6, d 15

Neuropathy continues; brentuximab held

PET/final restaging

Negative

• Neuropathy resolved; no limitations by 6 months post-treatment