Hodgkin Lymphoma: Discussing Toxicity With Patients

Leo Gordon, MD:As we go through decision making about choices of chemotherapy regimens, I think one should try to spend a fair amount of time going over potential short-term and long-term toxicities. We do see late cardiac toxicity sometimes. Using bleomycin, we can see lung toxicity. We can see infertility with all of these regimens, but I’m not certain we have a good database when we use brentuximab on the incidence of infertility. We know that with ABVD [doxorubicin/bleomycin/vinblastine/dacarbazine], infertility occurs in younger patients, people in their 20s, maybe 10% to 20% of the time. As patients get older, in their 30s and 40s, that number goes up. We routinely recommend either sperm banking or egg harvesting in men and in women of childbearing age, given the possibility of infertility.

We have a discussion about potential long-term toxicities. We do have a survivorship program at our institution where. I like to call it a long-term follow-up program at our institution, rather than a survivorship program. But I think it’s useful because these patients who are going to be 5 to 10 to 15 to 20 years out are going to be followed with their primary care physicians. It’s good to have good communication between the oncology group and their primary care physicians, because the primary care physicians may be the ones noticing some of these late toxicities.

We haven’t seen second malignancies as a prominent feature in patients getting ABVD. We don’t have enough data to say anything about brentuximab. We do know from early Hodgkin lymphoma studies that regimens like MOPP [mechlorethamine/vincristine/procarbazine/prednisone] were associated with a higher risk of secondary malignancies, especially acute leukemia, and so those are concerns. We don’t have a lot of information yet on brentuximab because it’s brand new in first-line treatment.

First of all, our patients are seen regularly. We usually see patients on a regimen such as this one, which is a day one 1, day 15 regimen, on day 1 of each cycle. We see them once a month. On day 15, they’re seen by our nurses, our nurse practitioners, or both. They’re encouraged to describe potential toxicities so they’re not missed. You can sometimes see mild neuropathy progressing to more severe neuropathy over time. If it’s not recognized, you may lose the opportunity to mitigate a dose toxicity.

We really encourage patients to communicate with us about any unexpected symptom. We usually describe and give them a handout regarding what symptoms to expect, and they’re encouraged to tell us about anything that deviates from that or anything that is on that list, really.

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