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.