Comorbidities and Rituximab-Based Therapy in FL

Nathan H. Fowler, MD:After we determine that a patient needs treatment, the next step is to figure out what is the treatment that is best for this patient. This often involves a discussion with the patient about the risks and the benefits of different treatments, about the different progression-free survivals or remission times with different treatments. But, also, it really involves a discussion and a close look at the comorbidities of the patient when they present for therapy.

Now, in this patient, she has neurogenic bladder and osteoporosis. I think those are not hard-and-fast determinants of a different type of treatment. But, for example, in a patient who had a history of cardiac disease, we might want to avoid anthracyclines in patients who have significant neuropathy. Peripheral neuropathy, for example, from diabetes, we might want to avoid a vincristine-like molecule. In patients who have a history of blood clots, sometimes we avoid drugs like lenalidomide. But, again, this is really a detailed discussion with the patient about the risks and benefits of different therapies.

Rituximab is really one of the landmark drugs that led to an improvement in survival in patients with follicular lymphoma. And we’ve seen with multiple studies, including multiple randomized studies, over the past really couple decades, that adding rituximab to chemotherapy—these are often combination chemotherapy backbones—has been shown to improve not only remission times but also overall survival. And really in most of the regimens that we use today for both newly diagnosed and for relapsed follicular, we include rituximab.

Recently, we saw the introduction of subcutaneous rituximab into the market in Europe, as well as in the United States. Subcutaneous rituximab has been shown to be equivalent to intravenous rituximab in a couple big randomized trials. One of those was the SABRINA trial, which looked at subcutaneous rituximab compared to intravenous rituximab with a chemotherapy backbone in follicular lymphoma. And in that study, we saw that the outcomes were pretty much identical with regards to remissions and overall response rate.

So, in my mind, I think that they’re essentially equivalent with regards to efficacy. The differences between these 2 agents are the route of administration and some of the side effects. Clearly, like its name, subcutaneous rituximab is given subcutaneously. For folks who are using this in the clinic, I think it’s important to remember that this should only be given on the second exposure to rituximab, so patients should still have intravenous rituximab for the first infusion. If they don’t have a significant reaction to intravenous rituximab, they can then receive subcutaneous rituximab on the second exposure. This should really only be given in the abdomen. Patients should be watched for about 15 minutes after the infusion; patients can develop redness and a local reaction at the injection site.

But, otherwise, I think it’s fairly well tolerated. Clearly, giving a drug subcutaneously allows us to get a patient out of the clinic a little bit faster. I think patients generally enjoy not sitting in the infusion center quite as long. But, again, I think like any change in therapy, this should really be discussed with the patients, the pros and the cons, along with the potential side effects.

Transcript edited for clarity.

June 2015

• A 65-year old female presented to her PCP complaining of night sweats and swelling in the neck
• PMH: osteoporosis, neurogenic bladder
• Physical examination:
  • Enlarged spleen 2 cm. below costal margin, bilateral cervical and axillary lymphadenopathy
• ECOG 0
• Laboratory findings:
  • WBC: 12 x 10⁹/L; 45% lymphocytes
  • Hb: 11.5 g/dL
  • Platelets: 213 x 10⁹/L
  • LDH 212 U/L
• Excisional biopsy of the lymph nodes:
  • IHC: CD10+, BCL2+
  • Follicular lymphoma, grade IIIa
• Bone marrow biopsy, 40% involved
• ¹⁸FDG-PET showed SUVmax of 9 with discrete masses bilaterally in the cervical and axillary region and increased uptake in the liver
• FLIPI 4 points, high risk
• The patient was started on bendamustine + rituximab (6 cycles) and was continued on rituximab maintenance therapy for 12 months
• She achieved a partial response with a 75% reduction in tumor volume

February 2018

• After 32 months, the patient complained of her symptoms returning
• CT showed disease progression in the axillary and hilar lymph nodes
• PET with SUV of 11
• Re-biopsy of lymph node, consistent with follicular lymphoma grade IIIa
• The patient was referred to an academic center for treatment
• She was enrolled in an open-label clinical trial of lenalidomide/rituximab (12 cycles)
• She achieved partial remission after 3 months

February 2019

• Twelve months later, the patient presents with low-grade fever and chills, she is otherwise well-appearing and continues to exercise regularly
• ECOG 0
• PET-CT showed further progression in the axillary lymph nodes
• The patient was treated with IV copanlisib and achieved a partial response after 4 cycles; she continues to do well on therapy