Early Relapse After Second-Line Chemoimmunotherapy in FL

Christopher R. Flowers, MD:Well, thank you for the opportunity to talk about this case. So this is a 75-year-old woman who presented with severe fatigue and weight loss. She initially was diagnosed with large lymph nodes in the inguinal region, having contiguous stage II follicular lymphoma, and that was about 4½ years ago. She completed initial therapy with bendamustine-rituximab and achieved a partial response, and that partial response [PR] persisted for almost 4 years.

Then she ultimately relapsed with disease and started on treatment with the combination of R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone] when she had extensive mediastinal follicular lymphoma. That was approximately 6 months ago and having achieved a PR, that PR lasted only 3 months this time before her symptoms returned.

Other than her follicular lymphoma, she has a history of type 2 diabetes that’s been going on for about 10 years and was controlled with basal insulin and with oral therapy. And at present she now has swelling in her right axillary lymph node that’s not tender to touch. On physical exam she doesn’t have any other abnormalities, with no history of pneumonia and a normal lung exam.

She’s received her usual flu vaccinations and a Pneumovax. And at present her ECOG [Eastern Cooperative Oncology Group] Performance Status is 1.

At her time of relapse she had a biopsy, and that biopsy demonstrated evidence of follicular lymphoma grade 2. And there was no evidence of transformation to diffused large B-cell lymphoma. She had routine laboratory examination performed that showed no evidence of transaminitis. She had a glomerular filtration with a rate of 72 mL/min and an absolute neutrophil count of more than 1000, at 1350. Her platelets were 100,000. She had a hemoglobin [level] of 10 [g/dL] and an LDH [lactate dehydrogenase level] of 275 [U/L]. On routine imaging with [a] PET/CT [positron emission tomography or computed tomography] scan, that demonstrated evidence of axillary lymphadenopathy with her largest lymph node mass being 7.2 cm; with SUVs [standardized uptake values] that were in the range of a 4 to 9, with none of them being remarkably elevated.

She was started on idelalisib with 150 mg twice daily. And after 10 days of therapy she called with evidence of diarrhea and was experiencing on average about 4 loose stools over the last few days.

So this is a fairly typical woman who presents with follicular lymphoma at the outset. The average age at diagnosis for patients with follicular lymphoma is on the order of the late 60s to early 70s, and the kinds of therapy we typically use in the United States right now would be bendamustine-rituximab as the most commonly used initial therapy.

There are newer data using obinutuzumab as a combination with chemoimmunotherapy. And R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone] and possibly lenalidomide plus rituximab can be other alternatives that can be used currently. At the time that she was diagnosed, bendamustine-rituximab would be the most commonly used therapy during that time frame.

It’s a little bit unusual that after such a prolonged response to bendamustine-rituximab that she had such a short interval to response to second-line therapy with R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone]. We do see after first-line therapy that approximately 20% of patients with follicular lymphoma have a short interval after their initial therapy where they require a second therapy. That’s been well described by Carla Casulo as the so-called early relapsing follicular lymphoma, [in which] relapse occurs within 2 years. She actually had a fairly typical initial response to therapy but early relapse after second-line therapy.

Those early relapses after second-line therapy [have] not been as well characterized, but that suggests that her response to any further form of chemoimmunotherapy is unlikely to be of great benefit, particularly after having a short response to R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone].

So it’s a little bit unusual for that to happen, for her to progress that rapidly after second-line therapy. Right now we’re trying to fully characterize those patients in a number of studies. There is a randomized control trial after first-line therapy looking at patients who have early relapsed. And that population is led in a trial by Paul Barr, [in which] I’m the ECOG lead for that trial, along with Brian Link. And hopefully in that population we’ll also characterize the genomics of those patients, as well as using something like the M7 FLIPI [Follicular Lymphoma International Prognostic Index] to try [to] identify prognostic factors. As of yet, we have clinical factors, which are typically the clinical factors that are used in the FLIPI Index that helped to identify those early-relapsing patients. But for the vast majority of patients, we have not yet identified reasons why they may relapse early after chemoimmunotherapy.

Transcript edited for clarity.

Case:A 72-Year-Old Woman With Relapsed Follicular Lymphoma

H & P:

• A 75-year-old woman presented with severe fatigue and weight loss
• Was diagnosed with inguinal contiguous stage II follicular lymphoma (FL) 4.5 years ago; completed BR and achieved PR that persisted for almost 4 years
• Started treatment with R-CHOP for extensive mediastinal FL 6 months ago; had achieved PR by 3 months before symptoms returned
• PMH: Type 2 diabetes X 10 years, controlled on basal insulin and SGLT2 inhibitor
• PE: Swelling present in right axillary lymph nodes; not tender to touch; no crackles or rales in lungs; no history of pneumonia; has received flu and PPV23 vaccination
• ECOG performance status: 1
• Biopsy showed grade 2 FL without transformation
• Labs:
  • eGFR = 72 mL/min/1.73²
  • AST/ALT: within normal range
  • ANL: 1350 /mm³
  • Platelets: 100,00 /µL
  • Hemoglobin: 10 g/dL
  • LDH: 275 U/L
• Imaging: PET/CT revealed axillary lymphadenopathy, with largest mass 7.2 cm
• She was started on idelalisib 150 mg b.i.d.
• After 10 days, she called with concerns about diarrhea, which she has been experiencing on average 4 times daily for the past few days