Immunotherapy beyond cellular therapy in Follicular Lymphoma: A case of complete remission after failure of two CAR-T
Adam M. Kase, M.D.1, Mohamed A. Kharfan-Dabaja, M.D.2, Andrew Donaldson R.N.1, Jamie Elliott APRN, D.N.P.1, Taimur Sher, M.B.B.S, M.D.1
1Mayo Clinic Florida Division of Hematology Oncology
2Mayo Clinic Florida Division of Hematology Oncology, Blood and Marrow Transplantation and Cellular Therapies Program
Adam Kase: kase.adam@mayo.edu, Mohamed Kharfan-Dabaja: kharfandabaja.mohamed@mayo.edu, Andrew Donaldson: Donaldson.andrew@mayo.edu, Jamie Elliott: Elliott.jamie@mayo.edu, Taimur Sher: sher.taimur@mayo.edu
Data Availability: The data that support the findings of this study are not publicly available due to privacy or ethical restrictions.
The authors have no conflicts of interests.
Patient consent was obtained for the publication of this case report.
No funding was provided for this manuscript.
Introduction:
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma which is known for its relapsing-remitting disease course with 20% of patients developing progression of disease within 2 years of chemoimmunotherapy.1 The treatment for relapsed follicular lymphoma includes combinations of chemoimmunotherapy, immune modulators and hematopoietic stem cell transplant. More recently chimeric antigen receptor T-cell therapy (CAR-T) has demonstrated impressive activity in the relapsed/refractory setting leading to the FDA approval of axicabtagene ciloleucel in February 2021 for relapsed or refractory follicular lymphoma.2 Patients not responding to CAR-T or relapsing soon after treatment have a poor outcome. 3 The optimal treatment for such CAR-T treatment failure remains unclear. Here we present a case of relapse refractory follicular lymphoma who relapsed after multiple lines of chemoimmunotherapy including two CAR-T infusions, who then achieved a complete remission after treatment with obinutuzumab and lenalidomide.
Case Report:
The patient is a 73-year-old female who was diagnosed with stage IVA follicular lymphoma in 2000. Over a period of 20 years, she received the following treatments with variable responses (Table 1), including: cyclophosphamide, vincristine and prednisone, followed by multiple rounds of rituximab, targeted radiation, a clinical trial with everolimus, single agent lenalidomide, an oral PI3K delta inhibitor on a clinical trial and rituximab plus gemcitabine with oxaliplatin. Despite all these therapies she continued to progress. She was enrolled in ZUMA-5 clinical trial for treatment with axicabtagene ciloleucel CAR-T and obtained a complete remission that lasted for approximately 1.5 years. At relapse, she underwent a second CD19 CAR-T in June 2020 and had florid progression of disease just two months later in August 2020 (Figure 1A). She briefly enrolled on a clinical trial with a novel BCL-2 inhibitor but had rapid disease progression within few days. In October 2020, she was started on obinutuzumab and lenalidomide. The dose of lenalidomide had to be reduced from 20 mg (days 1-21) to 5 mg (days 1-14) due to thrombocytopenia. A PET scan was obtained to assess response to treatment after 2 months and revealed radiologic complete remission. Ongoing surveillance PET scan (Figure 1B) in April 2021 showed continued remission, consistent with a 6-month durable radiologic complete remission after 5 cycles of obinutuzumab and lenalidomide two weeks on one week off.