Stage IIIa Hodgkin Lymphoma: Experience and Expectations

Leo Gordon, MD:Our experience with patients who are smokers over the age of 50, in the days when we were still not smart enough to use bleomycin, has been problematic, because these patients really develop significant bleomycin lung injury. Years ago, when we began noticing that and the data on predicting risk for bleomycin lung injury were published and out there, we stopped using bleomycin in that setting. And then we began in our clinical trial, where we gave brentuximab as a lead-in, and we saw basically no lung injury and very little neuropathy. The use of this particular regimen, ABVVD [doxorubicin/brentuximab vedotin/vinblastine/dacarbazine], is relatively new.

We have some experience with it in patients, but because it hasn’t become a standard regimen for us, we don’t use it in a lot of patients. We recently treated several patients with the regimen and have seen the toxicities that are being described in this particular case: febrile neutropenia, fevers, something we just didn’t see before with ABVD. I think there’s a learning curve with any new regimen. Everybody who participated in the study now has some experience. But I think as this becomes more routinely used in clinical practice around the country and around the world, we’re going to develop a better understanding of the potential risks and toxicities of this regimen.

This patient had what appears to be a complete response measured by a PET [positron emission tomography] scan after the second cycle that would predict for a very high likelihood that she won’t recur. I would say she has a 70% or 80% chance of long-term survival without any disease. I think this patient should do quite well.

Are there alternatives if she does recur? There are. We have excellent outcomes in stem cell transplantation in patients who relapse. Just to let you know where we are currently, based on the data published with the use of checkpoint inhibitors in patients with relapsed or refractory [Hodgkin] lymphoma, it looks like response rates in the order of 80% percent, although complete responses are only about 20% to 30% percent. We’re beginning a clinical trial looking at the use of pembrolizumab, or Keytruda, which is the checkpoint inhibitor from Merck. We’re using that as a lead-in followed by AVD [doxorubicin/vinblastine/dacarbazine] chemotherapy in patients with both early stage and advanced stage Hodgkin lymphoma.

We’re going to be presenting some of those data at the ASH [American Society of Hematology] meetings in Cologne with the German Hodgkin Study Group, and there were fairly impressive up-front responses measured by PET scan before any chemotherapy was given—just with the use of pembrolizumab—and so we’re very excited about those data. We have too few patients to make any major conclusions, but that study is continuing accrual. I think as we look forward to the next phase of treatment of Hodgkin lymphoma, it’s going to include the use of checkpoint inhibitors. That’s a prediction, but we’ll have to wait and see.

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