Approaching a Case of Stage IIIa Hodgkin Lymphoma

Leo Gordon, MD:We have a 52-year-old woman, a longtime smoker, who presented with abdominal pain. Evaluation on physical exam revealed right cervical adenopathy, and a CT [computed tomography] scan, which was done to evaluate the abdominal pain, revealed mediastinal adenopathy and abdominal adenopathy. A PET [positron emission tomography] scan confirmed those findings. She was found, therefore, to have clinical stage IIIa disease. A biopsy of the right cervical node revealed nodular sclerosis, Hodgkin lymphoma, which is classical Hodgkin lymphoma. At the end of staging, she had stage IIIa disease. She had no b symptoms: no weight loss, no fever, and no night sweats. She had a long history of smoking but no significant cardiac disease and no significant pulmonary disease.

She was treated with combination of Adriamycin [doxorubicin], brentuximab vedotin, Velban [vinblastine], and DTIC [dacarbazine], or the ABVVD chemotherapy regimen, as outlined in the recently published ECHELON trial comparing ABVD, which we consider to be a standard treatment approach in Hodgkin lymphoma, with ABVVD, which substitutes brentuximab vedotin for bleomycin in Hodgkin lymphoma.

Now, that trial resulted in an improvement in progression-free survival both internationally and, especially, in the recently evaluated North American cohort. There was improvement in progression-free survival but no benefit up till this point in overall survival.

This patient had a fairly typical treatment course, but that was complicated by a variety of toxicities. She had, after cycle 1, day 1, significant neutropenia with fevers. She was hospitalized for at least a week with febrile neutropenia, which is something we don’t really see in the ABVD regimen. In our experience with close to 100 patients at our institution, in data we published several years ago, the incidence of febrile neutropenia with ABVD was 0.4%, so we really see very little of febrile neutropenia.

One of the considerations—one of the concerns—in the substitution of brentuximab vedotin for bleomycin is that if you’re going to use that regimen, you are going to see a higher incidence of febrile neutropenia. I think in that setting, it becomes more important to consider the use of growth factors. Now, one might ask the question, “Which patients are most appropriate at initial diagnosis to consider for this regimen versus the standard ABVD regimen? Should it be all patients based on improvement in progression-free survival, or should it be a selected subgroup of patients?”

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