Sequencing Therapy in Follicular Lymphoma: Making Goal-Oriented Conversations Routine

Sponsored by Incyte

The follicular lymphoma (FL) treatment paradigm is characterized by rotating cycles of remission and relapse, and in some cases, refractory disease. Although FL is often indolent with prolonged survival, it can be difficult to treat due to its tendency to relapse, need for multiple lines of therapy, emergence of treatment related side effects and potential to transform into diffuse large B-cell lymphoma (DLBCL), a more aggressive disease.^1,2

Given the risk of relapse or refractoriness following first-line therapy – and the reality that many patients will require subsequent treatment(s) – having multiple effective options is central to durable disease control. A key challenge I hear from colleagues is how to sequence therapies to best help control the disease, while potentially minimizing toxicity, and how we may possibly help guide patients so that they can navigate their daily decisions and activities. My suggestion: have regular, goal-oriented conversations and refine treatment plans as patient priorities evolve.

How to structure and implement routine goal-oriented conversations

While each patient's experience is unique and their goals can change throughout different stages of their journey, I find it can be helpful to normalize these discussions and revisit them at key decision points. It allows me to clarify what trade-offs a patient is willing – or unwilling – to make when considering a different intervention, changing therapy, addressing toxicity and/or when a patient brings up new concerns. Even in time-limited appointments, a brief, repeatable “goals check” can help improve alignment and possibly adherence over time.

Through these conversations, I’m able to obtain clarity on the following:

• What are the patient’s top priorities and how would they like our help to potentially support (e.g., energy, ability to work, travel)?
• Any near-term and longer-term milestones that are top of mind (e.g., birthday celebrations, weddings, vacations, caregiving responsibilities) that may impact care?
• What type of treatment and monitoring schedule is realistic (e.g., visit frequency, labs, imaging)?
• Which potential toxicities are possibly acceptable or manageable?
• How does the patient weigh disease control vs. day-to-day functioning at this stage?

These answers then inform treatment sequencing and may help for a tailored approach that potentially aligns with clinical needs and real-world feasibility.

Sequencing after relapse: Balancing efficacy, safety, and potential feasibility

When a patient relapses or becomes refractory after first-line therapy, sequencing decisions can be informed by three areas:

1. Disease-specific factors including time to relapse/progression, grade, proliferation, evolving biology, and existing molecular or genetic mutations.
2. Patient-specific variables such as their age, any comorbidities, unresolved prior toxicities and concomitant medications.
3. Practical constraints like their distance to clinic, caregiver availability, monitoring schedule and financial or insurance considerations.

To help patients understand treatment sequencing without feeling overwhelmed, I often use the analogy that treatment is a "chess match" against the cancer: for every move we make against the disease, there may be a countermove in the form of potential side effects. I find that this framing supports shared decision-making and helps my patients understand why sequencing is a careful consideration.

Consideration of a potential treatment option

Treatment decisions in FL should be guided by goal-oriented conversations that account for individual patient priorities and overall treatment goals. In the second-line setting, chemotherapy is often considered, but it may impact patients’ quality of life.³ For appropriate patients, an outpatient option to consider is MONJUVI® (tafasitamab-cxix) in combination with rituximab and lenalidomide (R2), which is indicated for the treatment of adult patients with relapsed/refractory (r/r) FL. MONJUVI plus R2 is the first FDA-approved CD19- and CD20-targeted immunotherapy combination for this patient population.⁴

The efficacy and safety of MONJUVI plus R2 were evaluated in inMIND, a global, randomized, double-blind, placebo-controlled Phase 3 trial in 548 adult patients with r/r FL Grade 1, 2, or 3a after at least 1 systemic therapy, including an anti-CD20 antibody. Patients were randomized 1:1 to receive 12 cycles of MONJUVI plus R2 or placebo plus R2. Patients who received MONJUVI in combination with rituximab and lenalidomide achieved a median PFS by investigator assessment of 22.4 months (95% confidence interval [CI], 19.2-not evaluable [NE]) compared to 13.9 months (95% CI, 11.5-16.4) in patients treated with rituximab and lenalidomide (hazard ratio [HR]: 0.43 [95% CI, 0.32-0.58]; P<0.0001).⁴

In the inMIND trial, adverse reactions that occurred more frequently (>5% difference) with MONJUVI plus R2 vs R2 alone included COVID-19 infection, pneumonia, diarrhea, pruritus, fatigue, musculoskeletal pain, and mucositis.⁴

In the MONJUVI arm, serious adverse reactions occurred in 33% of patients, including serious infections in 24% of patients (including pneumonia and COVID-19 infection). Other serious adverse reactions in ≥ 2% of patients included renal insufficiency (3.3%), second primary malignancies (2.9%), and febrile neutropenia (2.6%).⁴

In my practice, I've seen the use of MONJUVI plus R2 emerge as a viable immunotherapy-based option for patients with relapsed or refractory FL.

MONJUVI is administered in the outpatient setting.⁴ MONJUVI should be administered with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions. For many patients, receiving therapy close to home may help reduce referral burden, support continuity of care and lessen caregiver and travel demands – important considerations for a disease that is managed over years.⁵

Ultimately, I believe we are moving toward a future where we manage FL as a chronic condition. That’s why I revisit treatment goals with my patients at each decision point and select therapies that support their individual needs. With evolving treatment options, I believe we are getting closer to providing a chance at remission that patients are seeking.

To learn more about MONJUVI, visit MonjuviHCP.com.

Please see Important Safety Information below and click here for Full Prescribing Information for MONJUVI.

INDICATIONS & USAGE
MONJUVI (tafasitamab-cxix), in combination with lenalidomide and rituximab, is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL).

Limitations of Use: MONJUVI is not indicated and is not recommended for the treatment of patients with relapsed or refractory marginal zone lymphoma outside of controlled clinical trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions
Infusion-Related Reactions
MONJUVI (tafasitamab-cxix) can cause infusion-related reactions (IRRs).

In inMIND, infusion-related reactions occurred in 16% of the 274 patients with FL who received MONJUVI in combination with lenalidomide and rituximab. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were generally managed with temporary interruption of the infusion and/or with supportive medication.

Premedicate patients prior to starting MONJUVI infusion. Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI. Institute appropriate medical management.

Myelosuppression
MONJUVI can cause serious or severe myelosuppression, including neutropenia, lymphopenia, thrombocytopenia, and anemia.

In inMIND, among 274 patients with FL who received MONJUVI in combination with lenalidomide and rituximab, new or worsening Grade 3 or 4 cytopenias included decreased neutrophils in 48% (Grade 4, 19%), decreased lymphocytes in 22% (Grade 4, 1.8%), decreased hemoglobin in 9%, and decreased platelets in 8% (Grade 4, 4%). Febrile neutropenia occurred in 4.4%.

Monitor complete blood counts (CBCs) prior to administration of each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor (G-CSF) administration. Withhold MONJUVI based on the severity of the adverse reaction. Refer to the lenalidomide prescribing information for dosage modifications.

Infections
Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose.

Among 274 patients with FL who received MONJUVI in combination with lenalidomide and rituximab in inMIND, Grade 3 or higher infections occurred in 24%, including fatal infections in 1.1% of patients. The most frequent Grade ≥ 3 infections were respiratory tract infections (19%), including Grade 3 or higher pneumonia (14%) and COVID-19 infection (11%). Opportunistic infections of any grade occurred in 6% of patients, including herpes simplex or zoster infection (5%), fungal pneumonia (1.1%, including Pneumocystis jirovecii pneumonia in 0.4%), and cytomegalovirus (CMV) reactivation (0.4%).

Monitor patients for signs and symptoms of infection and manage infections as appropriate. Consider infection prophylaxis per institutional guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIG) as appropriate.

Embryo-Fetal Toxicity
Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with MONJUVI and for 3 months after the last dose.

The combination of MONJUVI with lenalidomide and rituximab is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Adverse Reactions
In the MONJUVI arm, serious adverse reactions occurred in 33% of patients, including serious infections in 24% of patients (including pneumonia and COVID-19 infection). Other serious adverse reactions in ≥ 2% of patients included renal insufficiency (3.3%), second primary malignancies (2.9%), and febrile neutropenia (2.6%). Fatal adverse reactions occurred in 1.5% of patients, including from COVID-19, sepsis, and adenocarcinoma.

Adverse reactions led to permanent discontinuation of MONJUVI in 11% of patients and dosage interruptions in 74%. The most frequent adverse reactions leading to dosage interruptions of MONJUVI were neutropenia (37% of all patients), COVID-19 (22%), pneumonia (11%), and infusion-related reaction (8%).

The most common adverse reactions (≥ 20%) in people receiving MONJUVI were respiratory tract infections (56%) (including COVID-19 infection and pneumonia), diarrhea (38%), rash (37%), fatigue (34%), constipation (29%), musculoskeletal pain (24%), and cough (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 20%) were decreased neutrophils (48%) and decreased lymphocytes (22%).

Please see the full Prescribing Information for more information about MONJUVI.

MONJUVI is a registered trademark of Incyte.
Incyte and the Incyte logo are registered trademarks of Incyte.
© 2026, Incyte. MON-0014 08/26

References

1. Kaseb H, et al. StatPearls [Internet]. 2024.
2. Gupta G, et al. Am J Blood Res. 2022;12(4):105-124.
3. Johnson PC, et al. Adv Ther. 2024;41(8):3342-3361.
4. Incyte Corporation. MONJUVI [package insert]. 2025.
5. Thomson MD, et al. Cancer Med. 2023;12(16):17356-17364.