Case Presentation on Follicular Lymphoma

Case 1: Initial presentation

•A 74-year-old man complains of a 6-month history of fatigue, occasional fevers, decreased appetite, fatigue, and an

8-lb weight loss

•Previous Medical History: unremarkable

•Physical Examination: palpable right axillary and cervical lymph nodes, palpable ~ 3 cm in both

locations; spleen palpable 4.5 cm below left costal margin
 Questions
• What are the initial work up you will recommend?

• Will you start the start the therapy immediately or will you be in wait & watch mode?

• Upfront therapy, which drug will you choose?

• For how many years, patients are able to undergo first line regimen without
progression?

• Currently, what is your choice for Relapse refractory FL patients?

• Have you used Mosunetuzumab(BiTE - Bispecific T-cell engaging antibody) in FL

• Currently, your experience with Pi3k inhibitors?

• What is your opinion of using Idelalisib in your relapse refractory patients.

Clinical Workup

•Labs: 

•ANC 1.6 x 109/L, 

•WBC 11.2 x 109/L, 44% lymphocytes, 
•Hb 9.6 g/dL, plt 98 x 109/L, LDH 315 U/L, B2M 3.5 µg/mL;
•HBV negative
•Excisional biopsy of the axillary lymph node on IHC showed CD 20+, CD 3+, CD5+, CD 10+, BCL2+;
•follicular lymphoma grade 2

•Bone marrow biopsy showed paratrabecular lymphoid aggregates, 4% involvement

•Molecular genetics: t(14;18) (q32;q21)

•PET/CT showed enlargement of right axillary, cervical, and mediastinal lymphadenopathy (3.3 cm, 3.1, cm and 4.6 cm

respectively)

•Ann Arbor Stage IV; ECOG 0
Treatment

•He was treated with R-CHOP for 6 cycles, achieved complete response and continued rituximab maintenance

•24 months later he complained of increasing weight loss, fever and drenching sweats as well as more
enduring fatigue and new onset itching; he was currently taking antibiotics for his 3rd bacterial infection in the
past year
• Repeat PET/CT revealed progression of disease
• He was started on bendamustine + rituximab for 6 cycles and continued on rituximab maintenance
• Repeat lymph node biopsy grade 2 follicular lymphoma
•12 months later he complained of continued weight loss, increased itching and worsening fatigue; recurrent
infections continued
• He was started on idelalisib 150 mg PO BID

• Prophalyxis of Trimethoprim/sulfamethoxazole (Bactrim DS) is given

Case 2: Initial presentation

•A 76-year-old man complains of a 4-month history of bloating, fevers, and unintended weight loss of 9 lbs

•PMH: Medically-controlled hypertension, brittle diabetes, CABG 10 years prior

•SH: Lives by himself 2.5 hours from the clinic; only daughter lives out of state

•PE: palpable right axillary lymph nodes, ~ 3 cm and bilateral cervical lymph nodes, ~ 2 cm; spleen
palpable 4.5 cm below left costal margin
 Clinical workup
•Labs: ANC 1.6 x 109/L, WBC 11.4 x 109/L, 45% lymphocytes, Hb 9.5 g/dL, plt 96 x 109/L, LDH 426 U/L, B2M
3.4 µg/mL

•HBV negative

•GFR 59 ml/min

•Excisional biopsy of the axillary lymph node on IHC showed CD 20+, CD 3+, CD5+, CD 10+, BCL2+; follicular
lymphoma grade 2

•Bone marrow biopsy showed paratrabecular lymphoid aggregates, 42% involvement

•Cytogenetics: t(14;18) (q32;q21)

•Molecular testing: EZH2 wild type

•PET/CT showed right axillary, bilateral cervical, and mediastinal lymphadenopathy (3.3 cm, 3.4, cm and 2.6 cm,
and 3.2 respectively)

•Ann Arbor Stage IV; ECOG 1

Treatment

•He was treated with bendamustine and rituximab for 6 cycles, achieved complete response and continued
on rituximab maintenance
• Side effects included grade 2 diarrhea with BR

•16 months later he complained of fevers and chills with increasing frequency
• Repeat PET/CT revealed progression of disease
• He received R-CHOP for 6 cycles and continued on rituximab maintenance
•11 months later he had worsening fatigue and increased weight
loss and work up revealed progressive disease
• He was started on Idelalisib 100 mg BID

• Prophalyxis of Trimethoprim/sulfamethoxazole (Bactrim DS) is given

 Case 1 CLL: Initial Presentation:

• 71-year-old woman who was diagnosed initially with CLL in 2015

• trisomy 12. At the time, she was asymptomatic, so she was monitored without treatment.

• In 2 years she started to develop gradual symptoms, including some intermittent fever, increasing
fatigue, loss of appetite, and some weight loss.

• On exam, she was found to have increasing adenopathy.

 Questions
• Is Chemoimmunotherapy (CIT) still an option for CLL patients?

• What type of patients still you prefer CIT?

• What are the diagnostic work up will you recommend before initiating therapy? Is Identifying IGHV status also part
of the work up?

• Is Comorbidities play a role while choosing a therapy?

• What is the most common comordities you have seen in your CLL patients?

• What is your opinion of using Acalabrutinib as upfront in your CLL patients?

• Have you used Venetoclax in your CLL patients? At what dose used?

• In your relapse refractory patients, what is the regimen currently you will prefer?

• After BTKi failure, what is your opinion of using Idelalisib?

• For patients, who are not ideal fro BTKi, what is your opinion of using Idelalisib/
Labs:
• Starting to have some progressive cytopenias.

• At the time, FISH was repeated; she still had the trisomy 12 without any additional abnormalities.

• After discussion of treatment options, she was started on treatment with ibrutinib, standard dosage of 420
mg once a day.
• She was doing well for about a 1½ years

• she started having progressive increasing lymphocytosis, cytopenias, and adenopathy.

• At that time, the suspicion was that the disease might be progressing.

• Tests done to try to confirm whether she had developed ibrutinib resistance.

• Flowcytometry confirmed that she had relapsed CLL in the peripheral blood.
• Her IGVH was confirmed to be mutated.

• FISH showed that she still had trisomy 12. However, now she had acquired a new mutation, which is
aTP53mutation, a high-risk feature, which might be explaining her relatively short interval on the treatment.

• Her bone marrow biopsy showed that she had extensive involvement with CLL 84% in the bone marrow. At
that point, we believe she had developed resistance to ibrutinib and this treatment was stopped.
She was started with Idelalisib 150 mg BD

Prophalyxis of Trimethoprim/sulfamethoxazole (Bactrim DS) is given

 Case 2: Initial Presentation
• May 2014, 2 years after diagnosis, a 40-year-old female patient with CLL was admitted with relapsed disease

• initial immuno-chemotherapy with R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin, vincristine, and
prednisone) and FCR (i.e., fludarabine, cyclophosphamide, and rituximab) that ended in November 2013.

• She had marked lymphadenopathy, splenomegaly, severe anemia, hyperleukocytosis with lymphocytosis,
and mild thrombocytopenia.

• Peripheral blood flow cytometry analysis was consistent with CLL, bone marrow studies showed massive and
diffuse infiltration with clonal small B lymphocytes,

• FISH detected del 17 p in 38% of nuclei, indicating a high risk.

• She was initiated with Acalabrutinib as she has high risk features like TP53 and 17p

• She continued the drug another 3 years

• In Dec 2017, during her follow up, she started having progressive increasing lymphocytosis,
cytopenias, and adenopathy.

• Tests done to try to confirm whether she had developed Acalabrutinib resistance.

• Flowcytometry confirmed that she had relapsed CLL in the peripheral blood
She was initiated with Idelalisib 150 mg
• After 1 year, she has shown increased incidence of Diarrhea, she has been put on Anti-diarrhea drug.

• Idelalisib dose was reduced to 100 mg BID.

• Diarrhea incidence came down, she was on treatment for more than 3 year.

• Initial elevation of AST/ALT was observed, on close monitoring it came down after 12 weeks.

• Prophalyxis of Trimethoprim/sulfamethoxazole (Bactrim DS) is given