Understanding Patient Goals and Risk Factors When Determining Therapy for Newly Diagnosed and Recurrent/Relapsed CLL
Welcome to this Clinical Case Series learning module!
Here's how it works:
- Read these 3 case studies on the AP role in best practices for managing CLL.
- Answer the poll next to each case to see how your colleagues are managing these patients. You'll see results in real time.
- Continue your learning by watching a recording of a webinar presented by Sara M. Tinsley-Vance, PhD, APRN, AOCN
Endurance Athlete With CLL Recurrence After Chemotherapy
Clinical Pearl: Patient goals around quality of life can sometimes be managed using fixed-duration treatments.
A 78-year-old man was diagnosed with chronic lymphocytic leukemia (CLL) in 2005 when he presented with lymphocytosis on routine blood tests, without any symptoms. His complete blood count (CBC) showed a white blood cell (WBC) count of 14.9, a hemoglobin (Hb) level of 15.9 g/dL, and a platelet count of 218,000; lymphocytes were 70% of the differential. He was subsequently referred to a hematologist, who performed a bone marrow biopsy with aspiration and CT scans of neck, thorax, abdomen, and pelvis. Marrow revealed a normocellular marrow with 30% to 40% infiltration with CLL. Cytogenetics were positive for 13q deletion only. Flow cytometry was positive for CD20, CD19, and CD5. CT scans were negative for lymphadenopathy or splenomegaly. The patient was diagnosed with Rai stage 0, with good prognostic features. He was followed every 3 months without indication for treatment.
In 2013, his WBCs increased to 274,000 with an absolute lymphocyte count of 260,000, a Hb of 12 g/dL, and a platelet count of 135,000. He remained without symptoms, aside from a slight decline in exercise endurance. He developed palpable lymphadenopathy in the neck, axilla, and inguinal region, and some palpable splenomegaly was noted.
The patient was an endurance athlete actively participating in competitive rowing (including ocean) and cycling around the world. At that time, he verbalized that he would like to postpone treatment for CLL until he completed a series of competitive events, although he technically met the criteria to begin.
With enlarging bulky inguinal lymph nodes (right inguinal of 8.6 cm) that were interfering with his ability to row efficiently, he elected to begin treatment with chemoimmunotherapy. CT scans showed extensive lymphadenopathy within the neck, thorax, abdomen, and pelvis, and his spleen was enlarged to 18 cm. Repeat fluorescence in situ hybridization (FISH) was still positive for 13q deletion only. Treatment with fludarabine, cyclophosphamide, and rituximab was administered for six cycles, without complications, and a complete response was achieved.
He transitioned back to every-3-month observation and experienced an excellent quality of life, with the ability to exercise regularly and participate in competitive sports.
In 2018, the patient began to experience recurrent infections. He was hospitalized with pneumonia and treated with IV antibiotics. During admission for pneumonia, he developed atrial fibrillation. Subsequently he underwent ablation with a return to normal sinus rhythm. Within 6 months of developing recurrent infections, his WBC began to increase and was predominantly lymphocytes. At the next visit, recurrent lymphadenopathy was noted so PET/CT ordered, as well as FISH testing. The PET/CT was without bulky lymphadenopathy; FISH testing showed the 13q deletion, as well as a new 17p deletion in most cells. The patient was presented with two treatment options: chemoimmunotherapy with bendamustine and rituximab or fixed-duration venetoclax in combination with rituximab. The APP discussed existing data on both treatments with the patient, such as the MURANO trial,1,2 and he opted for venetoclax and rituximab because the fixed duration offered him the freedom to travel and be active. He received 6 months of combination venetoclax and rituximab and then venetoclax alone for 2 years.
This was the best treatment for this patient due to the definite start and stop. After treatment, the patient was able to participate in competitive rowing and cycling, which improved his overall health. He continued his life with minimal interruption in the activities that were enjoyable and meaningful to him.
Table: Laboratory Values in 2018
| Laboratory Parameters | Value |
|---|---|
| White blood cell count | 26,000 |
| Absolute neutrophil count | 21,000 |
| Hemoglobin | 13.2 g/dL |
| Platelet count | 120,000 |
| Quantitative immunoglobulins and IgG level | > 900 |
References
- Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378:1107-1120.
- Seymour JF, Kipps TJ, Eichhorst BF, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140:839-850.
Young Patient With High-Risk Disease Characteristics
Clinical Pearl: Following manufacturer instructions regarding the ramp-up period for venetoclax decreases the incidence of tumor lysis syndrome.
A 36-year-old woman presented with a 40-pound weight loss as well as flu-like symptoms, such as a sore throat, a runny nose, and a fever of 101.1° within the past week. A physical examination was remarkable for enlarged tonsils bilaterally, but there were no other noted abnormalities. Her only comorbid condition was asthma. There was no family history of cancers.
Table: Laboratory Values at Presentation
| Laboratory Parameters | Value |
|---|---|
| White blood cell count | 15.95K/µL |
| Hemoglobin | 14.5 g/dL |
| Hematocrit | 42.1% |
| Platelet count | 157 K/µL |
| Neutrophil count | 5.26 K/µL |
| Eosinophil count | 0.16 K/µL |
| Monocyte count | 1.12 K/µL HIGH |
| Lymphocyte count | 9.41 K/µL HIGH |
| Lymphocyte Percent | 59% |
Flow cytometry testing revealed B-cell monoclonal lymphocytosis consistent with CLL and was positive for CD5, CD19, and CD23. FISH testing revealed a 17p deletion in 47% of cells. No IGHV mutation was present.
The APP communicated to the patient that she had Rai stage 0 CLL and reviewed her high-risk molecular features. The discussion included an overview of data on 17p deletions and wild-type IGHV status, both of which make rapid disease progression and poor response to chemotherapy likely. Because the patient was premenopausal, the APP also discussed family planning, including fertility preservation. The patient’s age also triggered a discussion regarding potential germline predisposition. The patient was referred for genetic testing and was subsequently found to have somatic mutation, not germline.1
Within 6 months, the patient rapidly progressed with tonsillar enlargement, pulmonary infiltrates, and continued weight loss. Bronchoscopy was performed and biopsy was determined to be CLL and not infectious. The patient was also evaluated by head and neck physicians who thought the tonsillar enlargement was consistent with CLL as well. Because of the patient’s high-risk profile, combination venetoclax and obinutuzumab was initiated, as this combination has shown progression-free survival benefit for patients with unmutated IGHV.2,3
The patient underwent scans to determine whether she was at high risk for tumor lysis syndrome (TLS), and the venetoclax protocol for mitigating tumor lysis syndrome using a 5-week ramp-up period was initiated. The protocol included administration of allopurinol starting 3 days prior to administration of venetoclax and continued indefinitely. The patient was instructed to stay well-hydrated, and the APP provided an explanation as to what each appointment was for during the ramp-up period so she understood the value of the schedule. The patient underwent blood tests at pre-dose, 6-8 hours after each new dose during the ramp-up, and 24 hours after reaching the final dose to monitor for TLS.
Table: Recommended TLS Prophylaxis and Monitoring for Patients Initiating Venetoclax Based on Tumor Burden
| Tumor Burden | Prophylaxis | Blood Chemistry Monitoring | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Low: All lymph nodes < 5 cm AND ALC < 25 x 109/L |
|
Outpatient
|
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| Medium: Any lymph node 5 cm to < 10 cm OR ALC ≥ 25 x 109/L |
|
Outpatient
|
|||||||
| High: Any lymph node ≥ 10 cm OR ALC ≥ 25 x 109/L AND any lymph node ≥ 5 cm |
|
In hospital (at first dose of 20 and 50 mg)
Outpatient (at subsequent ramp-up doses)
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| Scroll to reveal full table | |||||||||
At the end of the dose titration, no evidence of TLS was found. The patient was referred for consideration of a blood and marrow transplant once the 17p deletion becomes undetectable. The APP and the patient discussed both immediate and long-term goals of care, including quality of life and avoidance of financial toxicity.
References
- Schienda J, Stopfer J. Cancer genetic counseling—Current practice and future challenges. Cold Spring Harb Perspect Med. 2020;10:a036541.
- Fischer K, Al-Sawaf O, Bahlo A-M, et al. Venetoclax and obinutuzumab in patients with CLL and coexiting conditions. New Engl J Med. 2019;380:2225-2236.
- Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5-year results of the randomized CLL14 study. Presented at: European Hematology Association, June 12, 2022. Abstract S148. Accessed August 30, 2023. https://library.ehaweb.org/eha/2022/eha2022-congress/357012/othman.al-sawaf.venetoclax-obinutuzumab.for.previously.untreated.chronic.html
Achieving a Complete Response Despite Disease Recurrence, Severe Infections
Clinical Pearl: Patient goals regarding side effect avoidance and management should be a primary focus during shared decision-making discussions.
A 62-year-old male was diagnosed with CLL Rai stage 0 in 2000, based on routine labs showing lymphocytosis and a 13q deletion. The patient had a history of malignant melanoma and hypertension. Observation was determined to be the best course of action.
In 2005, the patient’s complete blood count (CBC) showed a white blood cell (WBC) count of 240,000, a hemoglobin (Hb) level of 12.6 g/dL, a hematocrit level of 42.7%, and a platelet count of 300,000.
In 2008, a repeat CBC showed an increase in WBC to 428,000 and a decrease in both hemoglobin to 6.7 g/dL and the platelet count to 238,000; just 3 days prior, the patient’s Hb level was 8.6 g/dL. The absolute lymphocyte count was 406,000. The patient’s lactate dehydrogenase (LDH) level was high at 1,321 U/L. The results of the Coombs (antiglobulin) test was very positive (4+), indicating that the patient had developed acute hemolytic anemia. He was treated with high-dose steroids, transfused with packed red blood cells, and monitored carefully. Once the patient recovered from hemolytic anemia, treatment for CLL with fludarabine and rituximab was initiated. A complete response was achieved.
In 2009, the patient experienced a disease relapse, for which he was treated with three cycles of bendamustine and rituximab. Unfortunately, the patient was unable to proceed with the fourth treatment cycle because of neutropenia. PET/CT showed massive retroperitoneal and pelvic adenopathy, as well as numerous small cervical and axillary lymph nodes and splenomegaly. FISH testing revealed 71% nuclei positive for partial or complete ATM gene deletion and 5.3% nuclei positive for 13q deletion. A partial response to the three cycles of bendamustine and rituximab had been achieved.
Upon another disease relapse, the patient was treated with six cycles of pentostatin, cyclophosphamide, and rituximab, with a partial response at completion of therapy. Shortly after, the patient was hospitalized for approximately 1 year with severe, life-threatening, treatment-related infections.
Within 2 years of his extended hospitalization, the patient displayed signs of progressive disease, with bulky abdominal, retroperitoneal, and pelvic lymphadenopathy. A confluent mass in the mid-abdomen measured 20.6 x 11.0 cm. The patient expressed great concern about quality of life, as he was desperate to avoid a repeat hospitalization like the one he had endured with his previous treatment. The APP discussed the quality-of-life data available for single-agent venetoclax from the phase IIIb VENICE II trial.1 For the patients in this trial, the mean improvement in global health status was +9.3 points (n = 156, 95% CI: 6.1–12.5; p =.004). In addition, there were clinically meaningful improvements at Week 48 for role functioning, fatigue, and insomnia domains of EORTC Quality of Life Questionnaire (QLC)-C30.
The patient agreed to being treatment with venetoclax. Within 3 months of initiation of the highest dose (400 mg), complete remission was achieved and remains durable 9 years later.
Reference
- Cochrane T, Enrico A, Gomez-Almaguer D, et al. Updated quality of life data from the phase 3b VENICE II trial: Patients with relapsed or refractory chronic lymphocytic leukemia receiving venetoclax monotherapy. Leuk Lymphoma. 2023. DOI: 10.1080/10428194.2023.2247511
Meet the Faculty
Sara M. Tinsley-Vance
PhD, APRN, AOCN
Advanced Registered Nurse Practitioner
Moffitt Cancer Center
Sara M. Tinsley-Vance, PhD, APRN, AOCN is an advanced registered nurse practitioner working in the Department of Malignant Hematology at Moffitt Cancer Center since 2004. Prior to working in her current position, Dr. Tinsley worked in the Blood and Marrow Transplant department at Moffitt Cancer Center beginning in 1990. She frequently lectures at the University of South Florida and at Oncology Nursing Society Chapter meetings on hematologic disorders.
Let us know what you'd like to learn more about at jadpro-editor@broadcastmed.com