Susan Woodward: Okay. Case study three. Zanrha, you want to jump in for that?
Zanrha Esteban: Yes, so moving to case study three, AW is a 65-year-old patient with past medical history significant only for hypertension and squamous cell carcinoma involving his scalp. He does have refractory follicular lymphoma, diagnosed initially in 2011, with B symptoms with anemia and left hip pain. His CT scan of the chest, abdomen, pelvis showed extensive adenopathy as well as multiple lesions in his spleen.
We did a biopsy confirming his disease of follicular lymphoma grade 2. He received palliative radiation to his iliac bones because he was complaining of hip pain followed by R-CHOP x6 cycles and then transitioned to maintenance therapy for 2 years. He was noted with progression of disease in November 2014 with a PET scan showing disease in the neck, axilla and retroperitoneum. He was given 3 cycles of VR (venetoclax and rituximab).
He didn't complete 6 cycles due to side effects. His end-of-treatment CT scan showed residual disease in the left flank and right psoas area, so he received palliative radiation again to that area in May 2015. The PET scan in October 2015 showed marked improvement in the retroperitoneal mass.
Unfortunately, later that year he was found with symptoms of left-sided adenopathy. A PET scan showed evidence of recurrent hypermetabolic adenopathy in the neck, SUVs in the 12 consistent with relapsed disease. He saw our doctors here at Moffitt in March of 2015. Biopsy repeated, showed follicular lymphoma grade 1/2. Since the patient at this time didn't have any major symptoms, it was decided that observation was appropriate.
Later the next year, he was noted with progression of disease on his PET scan on August 19, 2016, with progressive hypermetabolic adenopathy. He developed also hip pain and MRI showed a right metastatic lesion on his iliac bone.
He was started on lenalidomide and rituximab in September 2016 because the patient did not want chemotherapy. PET scan after 2 cycles showed a very good PR (partial response). In 2017, he was referred to BMT (blood and marrow transplants) for a allogeneic stem cell transplant. He declined fearing the side effects, so he was continued on lenalidomide and Rituxan.
He was found with progressive disease on November 2017 with a PET scan showing areas in the cervical and mediastinal adenopathy as he was noticing enlarging lymph nodes in his cervical area. We did a biopsy again showing follicular lymphoma grade 1/2, with no evidence of transformation.
He was screened for a clinical trial CC-122 plus rituximab, but he failed screening due to thrombocytopenia. His platelets were less than 100,000. We did an NGS (next-generation sequencing), it shows the presence of TP53 mutation along with MYD88, MLL2, and CREBB mutations. There was no EZH2 mutation found.
So, he was given chlorambucil and rituximab in February 2018. He received 2 cycles. His PET scan showed a stable disease, so he was put on the ZUMA-5 trial with axi-cel (axicabtagene ciloleucel) for indolent lymphomas. He received his CAR-T infusion July 2018. There were some delays in his apheresis due to his platelets, though likely from his previous therapies. He developed CRS and neurotoxicity of grade 1. His day 30 PET scan showed CR (complete response) without any residual toxicities at this time and his repeat PET in May 2022 actually showed progression of hypermetabolic adenopathy in his cervical and mediastinal areas.
His bone marrow showed involvement in bilateral humerus and also right femur. So, he got a second CAR-T cell infusion on August 31, 2022, per ZUMA-5 axi-cel trial. He did a PET scan earlier this year in February, showed good response and then in May 2023 still showed remission with a very small residual mesenteric lymph node.
Our current plan for this patient is to continue observation.
Susan Woodward: I was going to ask about some of the factors that led to him wanting to, he did get about a 4-year response from that initial CAR-T so that's an excellent length of time where he was able to pursue his business. He's a local businessman, very focused on maintaining his work schedule throughout all of his treatments, and used to express that he wanted a one-and-done treatment so he'd get back to his regular life. So, I think that choosing a second CAR-T was a good option in his case and hopefully he'll have a good duration of remission this time.
Now, if he were to relapse in the future, is CAR-T again another option for him or what would we consider?
Zanrha Esteban: So, per trial parameters, we could only do CAR-T twice and actually talking with a PI (principal investigator) of this trial, he says that patients actually tend to respond better with a second CAR-T, so maybe he'll have a longer durable remission with a second CAR-T infusion.
Susan Woodward: So we could consider him to do bispecific antibodies, although he probably won't like coming back and forth?
Zanrha Esteban: No, but definitely an option, yes.
Susan Woodward: Okay. All right. And then your case study four.
Zanrha Esteban: So, our last case study is GC. He is a 58-year-old male with a past medical history, significant for PEs (pulmonary embolisms) and DVTs (deep vein thrombosis), hypertension. Did get rituximab-induced pneumonitis. His partner has HIV, but is on Truvada. History of pericarditis at the same time, with pneumonia in 2020.
He's very anxious. He has general anxiety disorder. He has gout, IBS (irritable bowel syndrome), hyperlipidemia and he has sleep apnea. He is on a CPAP.
So initially he presented in 2019 with dyspnea and chest pain and was found to have bilateral PEs and extensive left lower extremity DVT. During the management of his DVT, he was found to have extensive left inguinal adenopathy. The biopsy of his left groin was consistent with grade 1/2, follicular lymphoma, KI 67, about 5%, FISH- (fluorescence in situ hybridization) positive for that translocation t(14;18). NGS showed mutations that were not very significant and no BCL2 translocation and no EZH2 mutation at this time.
PET showed extensive hypermetabolic and enlarged lymph nodes above and below the diaphragm. Most hypermetabolic in the retrocrural space and retroperitoneal massive adenopathy was also noted. He was started with bendamustine Rituxan for 6 cycles. He completed it in 2019. He achieved PR (partial response) in transition to maintenance rituximab.
He was noted with progression of disease just shortly after starting maintenance rituximab in December 2019. We did another biopsy showing grade 1/2 follicular lymphoma. We also noted that he had toxicities with rituximab, so we did a lung biopsy showing rituximab-induced pneumonitis. So he was transitioned to obinutuzumab plus lenalidomide for about 10 cycles. In 2020, he experienced grade 1 diarrhea and issues with neutropenia and his treatment was interrupted several times and he only actually tolerated 10 milligrams of lenalidomide.
His interim PET showed a partial response, but was noted with progressive disease later that year in 2020 in December. He established care with us shortly in the beginning of 2021. We repeated his biopsy. There was really nothing crazy on his bone marrow, so we started him on tazemetostat in 2021, in March, but then later that year in September, he was noted with progression of disease in his CT NTAP (computed tomography scans for the evaluation of nontraumatic abdominal, back and flank pain) so he was referred over to CAR T-cell therapy.
In December 2021, he received Yescarta. Unfortunately, on his day 30, it showed persistent disease and then his day 60 scan showed increased metabolic activity in his lymph nodes and left external iliac biopsy was positive for follicular lymphoma.
So at this time, his clinical options were trials. He couldn't get off-the-shelf PB (peripheral blood) CARs since his day 30 showed no response. We didn't consider any IMID (Immunomodulatory imide drug) trials because of his significant cytopenias with lenalidomide.
We also discussed standard-of-care treatment with R-CHOP. He went ahead and enrolled with a bispecific TNB trial here at Moffitt. He was admitted for cycle 1 in June 2022, but later that year in November, he showed progressive disease and was taken off the study.
So we went ahead and did standard of care with R-CHOP with the ultimate goal of allogeneic transplant if he receive CR. If no CR, then we consider trial. So, he got 5 cycles of R-CHOP. His interim scans actually showed a complete metabolic response, so he went ahead and went to transplant with an allo on March 2023. So today he remains in CR. He does have some post-transplant complications with mild GVH with a rash. He is found to be hypogammaglobulinemia with recurrent infection. Most notable is that he keeps getting COVID pneumonia.
Susan Woodward: So, is he on chronic IVIG, Zanrha?
Zanrha Esteban: Yes, he is. And a lot of patient education throughout, every time he relapsed, with this patient, we went over that his disease was extremely aggressive and each time he received therapy, it'll be shorter each time he gets therapy. So ultimately, the only curative option for him was an allo. We didn't really consider an auto because it wouldn't be curative at that point and he was on board with it.
Given his age, he wasn't really, 58, he's pretty young. He does have a lot of comorbidities, but we worked with his primary care and also cardiologists making sure that we get all of those under control.
Susan Woodward: He's still interested in pursuing aggressive therapy?
Zanrha Esteban: Yes, he is.
Susan Woodward: Okay. So I think that the case studies that we presented kind of illustrated some of the typical side effects we see, some of the typical concerns that patients have where we take in their goals for their life, how significantly we're going to be impacting their quality of life by the treatment choices that we make and how complicated and long-term of a relationship we have with these patients that extend for years and years and multiple lines of treatment.
Amy, did you want to say anything about the relationships that you have with patients and that decision-making and support and we're really their person for so many years.
Amy Sidorski: Yes, I think it's true. Yes, I mean, we really develop relationships with them. We travel through their life with them and their family members. We meet them and develop relationships with them. So I think it becomes a partnership and we just kind of help guide them with data and our thoughts and recommendations, but let them kind of make the ultimate decision for what they want to do.
Then for some of our patients with more aggressive disease, then we certainly refer to the academic settings for CAR-T or transplant options.
Susan Woodward: This brings us to the end of our Follicular Lymphoma Roundtable Series. Zanrha and Amy, thank you so much for sharing your expertise with me and the viewers.
For more information and to view our other discussions on follicular lymphoma, please visit JADPRO online at jadpro.com.
