Monitoring Strategies in Follicular Lymphoma

EP: 1.Case Overview: A 60-Year-Old Man with Newly Diagnosed Follicular Lymphoma

EP: 2.Induction Therapy Options in Follicular Lymphoma

EP: 3.Follicular Lymphoma: The GALLIUM Study

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EP: 4.Monitoring Strategies in Follicular Lymphoma

EP: 5.Treating Early Relapse in Follicular Lymphoma

EP: 6.Follicular Lymphoma: Emerging Treatments

Alan Skarbnik, MD: For patients who are diagnosed with follicular lymphoma, I usually have a baseline laboratory imaging work-up. It is important to understand the tumor burden and have a benchmark for comparison post treatment to understand what degree of response the disease presented.

So obviously a CBC [complete blood count], a metabolic panel, LDH [lactate dehydrogenase], beta-2 microglobulin are important factors. If physicians have access to mutation panels, it does add prognostic tools to treatment, particularly with patients with more advanced disease. It does not really at this point guide the choice of therapy, but it is more information that may be useful, particularly for the intensity of monitoring following treatment.

I do prefer a PET [positron emission tomography] scan as the imaging modality for these patients. It gives me a better prognostic baseline at the end of treatment, so at the beginning of therapy compared to the end of therapy. After patients have finished the therapy, I do not customarily monitor with serial imaging. I will only do imaging if symptoms arise or there is obvious progression of disease on a physical examination or from patient history.

Early progression is the main concern for patients who receive treatment, particularly chemoimmunotherapy. There is significant evidence that progression of disease within 24 months [POD24] of finishing chemoimmunotherapy presents patients with a much poorer prognosis in terms of overall survival at that point, particularly for those who receive bendamustine as the backbone of therapy.

In induction, those who present with progression of disease within 24 months have a high rate of high-grade transformation to usually diffuse large B-cell lymphoma. It’s up to 76% in patients who present with POD24 and have received bendamustine as the chemotherapy agent in induction.

There are risk factors that may predict who will present with progression of disease within 24 months, or POD24. There are some that are more cumbersome. Now there are some prognostic models. There are some variables that are a little easier to do in clinical practice. For instance; FLEX [Follicular Lymphoma Evaluation Index], PRIMA-PI [PRIMA-Prognostic Index], m7-FLIPI [m7-Follicular Lymphoma International Prognostic Index]. Some of them require evaluation of the genetic mutation panel, including genes that are commonly mutated in follicular lymphoma.

Some of them use only a common laboratory work-up, such as PRIMA-PI, which uses beta-2 microglobulin to review if there is bone marrow involvement or not. Some use quantification of NK [natural killer] cells in the peripheral blood as part of the prognostication. They have different sensitivity, accuracy, and specificity levels between those prognostic models. As I said before, it depends on access to particular testing.

It is important to understand that baseline because it’s a discussion we can have with the patient. What are the risks? What are the concerns? How are we going to monitor the patient?

Following treatment, patients who do have a higher risk of early progression I tend to see in the office a little more frequently than patients who do not have those risks up front. But all these models need to be further validated prospectively, and they have been evaluated in different settings. Some of the models were evaluated in the setting where only CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or CVP [cyclophosphamide, vincristine, prednisone] were the backbone therapy. Other models included bendamustine and then were validated in a CHOP and CVP cohort. Some models only used rituximab as the anti-CD20 [antibody]. FLEX particularly included obinutuzumab in the GALLIUM study.

So there are differences, and a lot of times in clinical practice it is hard to pick one. It will depend on the patient and what regimen is going to be used. Largely, I would recommend picking a model that physicians will be familiar with, has ease of use, and can be used for most patients without necessarily having to add more complex and costly tests to evaluate these patients.

Transcript edited for clarity.

A 60-Year-Old Man with Follicular Lymphoma

Initial presentation

A 60-year-old man presents with a 4-month history of fatigue, decreased appetite, occasional fevers, and a 7-lb unintentional weight loss

PMH: Unremarkable

PE: palpable right axillary lymph nodes, ~2.5 cm and bilateral cervical lymph nodes, ~3 cm, spleen palpable 4 cm below left costal margin

Clinical workup

Labs: ANC 1.6 x 10^9, WBC 11.4 x 10^9, lymphocytes 42%, HB 9.7 g/dL, plt 97 x10^9, LDH 402U/L, 3.4 B2M ug/mL; HBV negative

Excisional biopsy of axillary lymph node on IHC showed CD20+, CD3+, CD5+, BCL2+, Follicular lymphoma grade 2

Bone marrow biopsy showed paratrabecular lymphoid aggregates, 38% involvement

Cytogenetics: t(14:18) (Q32;q21)

Molecular testing: EZH2 wild type

PET/CT showed right axillary, bilateral cervical, and mediastinal lymphadenopathy (3.1 cm, 3.1 cm, and 2.6 cm respectively)

Ann Arbor Stage IV, ECOG PS is 1

Treatment

Patient was treated with obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. He completed 6 cycles and treatment was well tolerated.

He continued on obinutuzumab maintenance.

19 months later, he complains of fevers, chills, and worsening fatigue.