Progression After R-CHOP: What Next?

John Pagel, MD:Responses to second-line R-CHOP are varied. Usually R-CHOP in the follicular lymphoma space is used as a frontline treatment, but some people will use it after failing bendamustine/rituximab. In those patients who have progression of disease in the first 24 months, as we’ve discussed, R-CHOP might give a response, but it’s going to give a very limited duration, just like we see here in this case.

The people [who] will do better with R-CHOP in the second-line are the people [who] had a long duration of remission to chemoimmunotherapy in the front line. So the longer the remission, the better chance that the R-CHOP is going to work.

The progression that this patient had is not typical for most follicular lymphoma patients, but it does happen. This is a very unique important situation to understand about how to approach these patients. That’s why I think idelalisib was a reasonable choice. Another option could have been in the right patient, and maybe in this patient, albeit he’s in his mid-70s, to do an autologous stem cell transplant. Although, it’s not typically something that we do in someone in their mid-70s.

The obinutuzumab is a very important drug to keep in the back pocket. Again, as I’ve said, this could be something that would be used here in this setting. I think once people relapse, if they’ve gotten prior anti-CD20 antibody treatment, getting more of that is certainly reasonable. And I think getting more obinutuzumab at time of relapse, even as a single agent, is not unreasonable in the right patient.

People will get a lot of rituximab; that’s how we treat patients with follicular lymphoma. Some of the patients, albeit it a relatively small number of patients, will become refractory to the anti-CD20 antibody treatment. If you re-biopsy patients, often they will be CD20 negative, suggesting that more rituximab won’t be particularly beneficial. I think those are patients in particular [who] we’re also going to want to really think about different ways of treating them. There is data suggesting then if you use idelalisib, like in this patient, if you’re refractory to rituximab, that it has good activity that can be relatively durable.

So like any time a patient relapses, we have to think of a lot of different parameters or factors that come into play when we want to figure out how we want to treat someone. Again, it comes back to the specific individual patient: how old they are, what their comorbidities might be, and what their treatment goals are. I think we make all of our treatment decisions on a system of mutual decision making with the patient and the family. It’s a commonly discussed topic, with all of those factors playing a role.

Transcript edited for clarity.

Case:A 70-Year-Old Man With Follicular Lymphoma

H & P:

• A 70-year-old man presents with night sweats and general fatigue
• PMH: hypertension, no history of MACE
• PE: Groin is tender to touch, no tenderness in abdomen
• Initially diagnosed with bilateral axillary contiguous stage II FL 5.5 years ago
  • Grade 2 FL, 4 masses (each >3 cm)
  • FLIPI status: high risk

Current biopsy and labs:

• Biopsy: grade 2 FL without transformation
• ECOG performance status: 1
• Hematologic results
  • ANL: 1200 /µL
  • Platelets: 105,000 /µL
  • Hemoglobin: 11.9 g/dL
• LDH: 335 U/L
• eGFR: 75 mL/min/1.73²
• Imaging: PET/CT reveals inguinal lymphadenopathy, with largest mass 8.5 cm

Treatment and disease history

• Front-line BR
  • Completed 6 cycles, achieved PR by 3 months
  • Maintained PR for 20 months before developing fever and mediastinal lymphadenopahty
• Second-line R-CHOP
  • Competed 6 cycles, achieved PR at 3 months
  • PR maintained for 5 months
  • Time since completion of last treatment: 5 months

Current treatment

• Started on single-agent idelalisib 150 mg twice a day