Blood Podcast: Review Series on Follicular Lymphoma

Host: Dr. Philippe Armand, American Society of Hematology
Guests: Dr. Carla Casullo, Dr. Sarah Rutherford, Dr. Aaron Perry
Date: October 30, 2025

Overview of the Episode

This bonus episode centers on the state-of-the-art in follicular lymphoma (FL), with a focus on relapsed/refractory disease, the future treatment landscape, and the critical issue of transformation. Dr. Philippe Armand moderates a vibrant discussion with three authors of the recent Blood review series: Dr. Carla Casullo (relapse/refractory treatment), Dr. Sarah Rutherford (future directions), and Dr. Aaron Perry (biology and transformation). The panel shares insights into current therapies, evolving advances (notably bispecific antibodies and CAR T-cell therapy), the promise of molecular monitoring, and the hope for functional cure.

Key Discussion Points & Insights

1. Treatment of Relapsed/Refractory Follicular Lymphoma

With Dr. Carla Casullo

• Bispecific Antibodies and CAR T-cell Therapy (01:48)

  • Major excitement surrounds bispecific antibodies, in use alone or with other drugs, and CAR T-cell therapy.
  • These targeted agents, previously reserved for patients post–second-line therapy, are advancing into earlier lines.
  • "To me, I think those represent probably one of the most important potentially practice-changing advances in this space." (Dr. Casullo, 02:33)

• Personalizing Therapy Selections (03:08)

  • Therapy selection in FL is inherently individualized, considering patient specifics, prior treatments, comorbidities, and duration of response.
  • Indolent lymphoma allows strategic, thoughtful decision-making. Patient quality of life and preference are integral to treatment choices.

• Role of Tumor Biology (04:08)

  • While genetic markers like EZH2 mutations may guide choices, overall molecular biology is not yet driving precise therapy due to limited actionable predictors.
  • "Biology...has even taken a bit of a backseat...I would love to be in that space very soon." (Dr. Casullo, 04:15)

2. Evolving Treatment Landscape & Future Directions

With Dr. Sarah Rutherford

• Frontline Bispecifics and New Combinations (05:00)

  • Multiple ongoing trials are evaluating bispecific antibodies, often with drugs like lenalidomide; these options likely to shift into frontline treatment soon.
  • Intent is to move away from more toxic chemotherapy (e.g., bendamustine) toward better-tolerated, effective options.

• CT-DNA Monitoring and Adaptive Treatment (05:50)

  • The field is moving toward using circulating tumor DNA (ctDNA) for guiding management and surveillance.
  • Potential for ctDNA-based de-escalation or re-initiation of therapy could personalize duration and timing, improving safety and flexibility.

• Therapy Sequencing and Multiple Lines (07:24)

  • As with rituximab, bispecifics may be reused in later lines for some, but for others, new strategies (e.g., tri-specific antibodies, NK cell targeting) are emerging.
  • CAR T-cell therapy holds potential for durable remission—and possibly cure—in select patients, though toxicity and aggressiveness remain considerations.
  • "In the last five years there’s just been an explosion." (Dr. Rutherford, 08:29)

3. Biology and Clinical Management of Transformation

With Dr. Aaron Perry

• Mechanisms of Transformation (09:10)

  • Transformation shares a clonal origin with FL but acquires additional genetic and microenvironment changes.
  • Advanced tools for studying patient-derived samples are deepening biological understanding, but much remains to learn.

• Strategies for Prevention and Intervention (10:17)

  • Key future challenge: predicting which patients will transform to enable proactive intervention.
  • Need to assess risk before first-line therapy and develop strategies for interception or prevention.

• Therapeutic Approaches for Transformed FL (11:57)

  • There is heterogeneity in transformed FL, and some will resemble large cell lymphoma subtypes. Current practice applies DLBCL (large cell) regimens, but future may bring divergence.
  • Aspirational vision: developing therapies that target the common progenitor cell to prevent transformation and relapse—a “holy grail” for achieving cure.

4. The Prospect and Concept of Cure in Follicular Lymphoma

Panel Discussion—Drs. Rutherford and Casullo

• Functional Cure vs. True Eradication (13:40)

  • Many patients achieve a “functional cure,” living long and well post-therapy, even if relapse status is not actively monitored.
  • Surveillance strategies emphasizing patient quality of life, with less aggressive testing in selected cases.

• Aggressive Disease & Curative Intent (14:40)

  • For young patients with high-risk or early-relapsing disease (e.g., POD24), more aggressive interventions—including trials with CAR T-cell therapy—are considered in pursuit of permanent remission.

• Transplantation in the Era of Novel Agents (15:46)

  • Autologous stem cell transplant is becoming rare in well-resourced settings, largely replaced by novel therapies.
  • Allogeneic transplant remains uncommon but may be appropriate in refractory, young patients; caution required due to high toxicity.
  • "Within the United States, I'm very infrequently recommending autologous transplant…very few and far between." (Dr. Casullo, 16:00)

Notable Quotes & Memorable Moments

• "I view indolent lymphoma as really a very strategic and thoughtful process because…we can be very thoughtful and selective…"
  — Dr. Carla Casullo, (03:11)

• "What I keep telling my patients that I’m so excited about, it’s been such a wonderful time to be in this field."
  — Dr. Sarah Rutherford, (08:23)

• "The holy grail, I think, of therapy as we think towards a possibility of cure."
  — Dr. Aaron Perry, (13:18)

• "[On transplant]...those treatments can come with the possibility of cure, but at a significant toxicity. So we have to weigh the balance very carefully so that we don't hinder someone's progress."
  — Dr. Carla Casullo, (16:17)

Important Segment Timestamps

• Overview and Series Introduction: 00:24–01:48
• Relapsed/Refractory FL Treatment & Personalization: 01:48–04:37
• Future Directions (Bispecifics, CT-DNA, CAR T): 04:37–08:42
• Transformation: Biology, Management, and Prevention: 08:42–13:26
• Cure & Advanced Therapies (CAR T, Transplant): 13:26–16:50

Tone and Takeaway

The conversation is collegial, optimistic, and deeply patient-centered, reflecting hope and excitement for rapidly expanding treatment options and the personal nature of care in FL. There is a clear sense of progress—“an explosion” of new approaches—and an undercurrent of anticipation for the next set of advances, especially regarding prevention of transformation and movement toward a true cure.

For Further Reading

Interested listeners are encouraged to explore the full review series published in Blood, as referenced throughout this discussion.