Watch-and-wait approach remains ‘reasonable’ for some patients with follicular lymphoma
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With new developments in the treatment of follicular lymphoma, such as chimeric antigen receptor T-cell therapies, whether the traditional watch-and-wait approach remains acceptable has been thrown into question.
In an interview with Healio, Jean L. Koff, MD, MSc, assistant professor in the department of hematology and oncology at Winship Cancer Institute of Emory University, discussed the benefits of the watch-and-wait approach, the patient population best suited for this approach and whether it still remains an effective option for treating follicular lymphoma.
Healio: What is the ‘watch-and-wait’ approach in follicular lymphoma?
Koff: Follicular lymphoma often behaves like a chronic condition, with patients experiencing long periods of relatively good health. The average overall survival after diagnosis is estimated at more than 20 years. Follicular lymphoma tends to grow slowly in most cases, and by the time the lymphoma is detected, 80% to 85% of cases are diagnosed with Lugano stage III or IV disease.
The watch-and-wait approach — sometimes also called “watchful waiting,” “observation,” or “active surveillance” — is a management strategy used in selected patients with follicular lymphoma and other indolent non-Hodgkin lymphomas that does not involve immediate treatment of lymphoma. Instead, patients are followed by their oncologists with periodic clinic visits, lab visits and imaging to monitor for signs and symptoms that indicate the need to start therapy. This strategy is used because advanced-stage follicular lymphoma is currently incurable with standard therapy, and we have more than 40 years of data showing that there is no survival benefit associated with earlier treatment initiation in patients who do not have a high burden of disease and remain asymptomatic.
Given that treatment will not provide a cure and many patients have a low burden of lymphoma that does not pose an immediate threat to their health, initiating treatment, which can induce short- and long-term toxicity, can be problematic in that setting.
Healio: Which patients benefit most from the watch-and-wait approach?
Koff: Patients with advanced-stage follicular lymphoma, a low burden of disease and a lack of symptoms from their lymphoma benefit from a watch-and-wait approach. The Groupe d’Etude des Lymphomes Folliculaires (GELF) criteria were developed to define patients who, by contrast, have a high burden of disease and, thus, should be considered for immediate treatment. These include:
- any node or mass 7 cm;
- 3 distinct nodal sites, each 3 cm in diameter;
- B symptoms (fevers, drenching night sweats and/or unintentional weight loss of > 10% of body weight over 6 months) or other symptoms attributable to the lymphoma;
- symptomatic splenomegaly;
- (impending) organ compromise;
- ascites or pleural effusion;
- elevated LDH or beta-2 microglobulin; and
- cytopenias attributable to the lymphoma.
For any patient with advanced-stage follicular lymphoma not meeting any GELF criteria, watch-and-wait should be considered to minimize unnecessary treatment-related toxicity. This might include newly diagnosed or previously treated patients.
Healio: What are some observations that would cause you to initiate treatment?
Koff: In addition to any of the GELF criteria listed above, rapidly growing lymph nodes either by patient report, physical exam or imaging studies should prompt a work-up to rule out transformation to an aggressive lymphoma such as diffuse large B-cell lymphoma and consideration of treatment initiation.
Down-trending hemoglobin or platelets without an alternative cause should prompt a bone marrow biopsy to determine whether bone marrow involvement by follicular lymphoma is the cause for cytopenias. Although B symptoms are the classic systemic symptoms associated with lymphomas, other symptoms attributable to lymphomas may depend on the site of involvement. For instance, although relatively uncommon in follicular lymphoma, lymphadenopathy that impacts the airway or gastrointestinal tract could cause associated symptoms.
Somewhat more commonly, bulky lymph nodes in cervical, axillary or inguinal chains may be uncomfortable or cosmetically unappealing. Often, patients who either present with or develop high-burden disease needing treatment will have a constellation of signs and symptoms that meet multiple GELF criteria (eg, bulky lymphadenopathy with worsening B symptoms).
Healio: What other approaches are used when monitoring follicular lymphoma?
Koff: PET scan or CT neck/chest/abdomen/pelvis should be performed at diagnosis to determine staging. Bone marrow biopsy should be performed in cases for which management would be impacted by lymphoma involvement of the bone marrow (eg, determining whether a patient has early-stage disease, whether cytopenias are attributable to their lymphoma).
For those patients with advanced-stage disease and not meeting any GELF criteria for immediate treatment, the watchful waiting approach includes oncologic clinic visits with history, physical exam and lab check (blood count with differential, complete metabolic panel and LDH) every 3 to 6 months for the first 5 years after diagnosis, and then annually thereafter, as long as follicular lymphoma continues to behave indolently. I typically schedule these visits every 3 months during the first year, every 4 months during the second year, and then every 6 months during years 3-5.
Patients should be counseled about the GELF criteria and encouraged to contact their oncologist should any concerning symptoms develop between visits. In terms of imaging, CT restaging is not recommended to be performed more frequently than every 6 months during the first 2 years after diagnosis, and no more than annually beyond 2 years, in the absence of signs or symptoms concerning for rapidly progressive disease.
Especially in patients with palpable lymph nodes who can be easily monitored on physical exam, I typically do not recommend frequent restaging because of the low likelihood that imaging findings will change management; more likely, frequent scans only serve to document indolent progression of disease and may be a source of anxiety for some patients.
Healio: In what situations would the watch-and-wait approach not be recommended?
Koff: Patients with Lugano stage I or contiguous stage II follicular lymphoma should not be managed with watchful waiting, but instead should be evaluated for involved site radiation therapy with curative intent. As detailed above, watchful waiting is not recommended for patients who meet any GELF criteria and/or have evidence for rapidly progressive disease. In addition, any patient with follicular lymphoma with grade 3b disease or transformation to an aggressive lymphoma merits immediate treatment.
Healio: Is this still an effective way to approach follicular lymphoma?
Koff: Yes, watch-and-wait remains a reasonable standard of care in the selected population discussed. Most patients with follicular lymphoma for whom therapy is deferred experience a treatment-free period of at least 2 years. Finally, watchful waiting represents an especially important consideration during the COVID-19 pandemic, since the B cell-directed therapies used to treat follicular lymphoma are expected to increase susceptibility to COVID infection and decrease the effectiveness of vaccines, thus increasing patients’ risk of COVID-19 infection and life-threatening complications.
As per the most recent update of the American Society of Hematology’s expert recommendations for managing indolent lymphomas in the setting of the pandemic, “the threshold for initiating treatment should be high, and watchful waiting should be the preferred strategy whenever possible. Treatment is recommended in symptomatic patients, but if the indication for therapy is borderline, (eg, if the patient meets GELF criteria but is asymptomatic) treatment deferral and close monitoring with repeat imaging may be prudent.”
Reference:
- American Society of Hematology. COVID-19 and indolent lymphomas: Frequently asked questions. Available at: https://www.hematology.org/covid-19/covid-19-and-indolent-lymphomas. Published: April 1, 2022. Accessed: June 1, 2022.
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