This article was originally published by Cure

Episode 3

Living with CLL as a Chronic Disease

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This article was originally published by Targeted Oncology

Ibrutinib (Imbruvica) during chimeric antigen receptor (CAR) T-cell culture improved the yield and function of CAR T-cell products as treatment of patients with chronic lymphocytic leukemia (CLL) in a study published in the International Journal of Cancer.

The study investigators led by Leapold Sellner, MD wrote, “our study provides evidence that BTK/ITK inhibition with ibrutinib during CAR T-cell generation may improve CLL patient-derived CAR T cell products and may have the potential to enhance CAR T-cell function. Ibrutinib-supplemented CAR T-cell production leads to increased CAR T-cell yields as well as enriches for less-differentiated T cells with lower expression of exhaustion markers and could be an option to further improve the clinical outcome of CLL patients.”

Sellner et al evaluated the absolute cell numbers during CAR T-cell generation by Trypan blue staining. During cell generation, cell proliferation was significantly lower in CLL-derived cells compared with HD-derived cells. The BTK inhibitor allowed for a significant increase in cell expansion of HD-derived cells on day 10 of the CAR T-cell generation (20.67 ± 8.82 × 106 without ibrutinib vs. 25.28 ± 10.29 × 106 with ibrutinib; P =.0248), and ibrutinib appeared to significantly increase the viability of CD3-positive T cells from HDs on day 10 (3% ±8% vs 87% ± 7%; P =.0183) and day 14 (84% ± 8% vs 91% ± 6%, respectively; P =.0202).

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This article was originally published by AJMC

Tumor mutational load (TML) can be used as a prognostic indicator in patients with chronic lymphocytic leukemia (CLL) and high-count monoclonal B-cell lymphocytosis (HC MBL), according to a new study.

The findings suggest that performing a focused mutation panel on recurrently mutated CLL genes could help risk-stratify patients and more accurately predict time to treatment (TTT).

Most patients who are newly diagnosed with CLL do not require therapy for a number of years, but some patients will require therapy right away. CLL’s precursor, HC MBL, will progress to CLL at a rate of 1-5% per year, but it can be difficult to predict how soon an individual patient will progress.

In hopes of better predicting patient progression, investigators from the Mayo Clinic conducted a study to analyze the total number of recurrently mutated CLL genes (TML) and the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed patients with CLL and HC MBL.

To do so, they recruited 557 patients, 445 of whom had CLL and the remainder of whom had HC MBL, and sequenced 59 genes in the patients. Their goal was to identify links with TTT, adjusted for CLL and sex.

The authors found that TML correlated with shorter TTT. Among patients with low/intermediate risk, the link was even stronger when patients were stratified by CLL-IPI. Their results are published in the American Journal of Hematology.

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This article was originally published by MedScape

The BALL score was able to identify a subset of patients with chronic lymphocytic leukemia (CLL) who particularly benefit from single-agent ibrutinib therapy, according to the results of a study of 111 patients followed from two different institutions.

The BALL model consists of four factors: serum beta₂-microglobulin at 5 mg/dL or greater, hemoglobin < 110 g/L for women or < 120 g/L for men, lactate dehydrogenase [LDH] > upper limit of normal [UNL], and time elapsed from last therapy less than 24 months. Each parameter was alloted 1 point, leading to a stratification of patients into three different prognostic groups: low risk (score 0-1), intermediate risk (2-3), and high risk (score 4), according to a report published online in Leukemia Research.

According to Stefano Molica, MD, of the Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues, the majority of patients (82%) were clinical Rai stage II-IV. The median patient age was 63 years and nearly 68% were men.

The researchers assessed four models for predicting overall survival. The modified version of CLL-International Prognostic Index (CLL-IPI) failed to provide prognostic information in relapsed/refractory (R/R) CLL (P = .77) as did the Ahn et al. model (P = .95) and a simplified BALL model (P = .09). In contrast, the full BALL score captured two groups of patients with significant differences in survival (hazard ratio, 0.240; 95 % confidence interval, 0.10-0.54; P = .0005); however, because of the low number of patients in the high-risk category, these cases were combined with the intermediate-risk group.

The BALL score identified a subset of patients, accounting for about 50% of the whole population, who particularly benefit from single-agent ibrutinib, according to Dr. Molica and his colleagues. These patients had a survival rate of 85% at 3 years.

“In contrast, the outcome of subjects with intermediate-high risk is disappointing. These patients should be considered for a combination of targeted drugs or cellular-based therapies,” the researchers concluded.

This article was originally published by Targeted Oncology 

During a virtual Case Based Peer Perspective event, Jonathon B. Cohen, MD, MS, the codirector of the Lymphoma Program, medical director of Infusion Servies, and associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and Winship Cancer Institute, discussed a case of a 71-year-old woman diagnosed with chronic lymphocytic leukemia.

Targeted Oncology™: What are reasonable treatment options to consider in a patient with CLL?

COHEN: The National Comprehensive Cancer Network guidelines offer 6 treatment options for patients with del(17p).¹ As I tell my fellows when I work with them, if you ever see a list of preferred regimens with 6 options, that likely means that nobody really knows what the best option is.

The 1 option not listed in the guideline is chemotherapy, especially in the relapsed setting for patients with del(17p). I generally would not use chemotherapy.

The only exception to that might be a situation where we have a patient who’s young and for whom we’re thinking about moving on to something like an allogeneic transplant or some other definitive therapy. We might consider using chemotherapy for a cycle or 2. But otherwise, if you’re not going in that direction, that’s the 1 thing we do feel comfortable saying—that is, that chemotherapy is probably not the right option.

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This article was originally published by AJMC

Adaptive Biotechnologies received its third approval from the FDA for the use of its next-generation sequencing assay to detect minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL).

The assay, clonoSEQ, uses a proprietary immunosequencing platform to monitor for MRD, where a small number of cancer cells remain during and after treatment. It is difficult to detect without precise, sensitive tools, and can lead to a recurrence of disease.

The approval follows a decision by CMS in January to pay for cloneSEQ testing for CLL, in addition to multiple myeloma and B-cell acute lymphoblastic leukemia. Nearly 80% of US patients with CLL are age 65 or over.

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This article was originally published by Pharmacy Times 

Chronic lymphocytic leukemia (CLL) is a cancer of the blood and bone marrow that can be treated to extend the life of some patients even by decades. Treatments and best practices are developing rapidly and health care providers need to stay up to date on all relevant information. In a Pharmacy Times Insights video series, a panel of experts discussed how to best treat and monitor patients living with CLL.

The panel included Alison Duffy, PharmD, BCOP, an associate professor and clinical pharmacy specialist in oncology at the University of Maryland School of Pharmacy and Cody Steeves, PharmD, BCOP, a clinical pharmacist for Biologics by McKesson.

Both intravenous (IV) and oral CLL medications are available, each with their own benefits and disadvantages. A combination method is also used by many patients, but that also presents a unique set of challenges.

“Some of the economic challenges we’ve seen have been the timely approval of the oral and the IV therapy together because of pharmacy benefits and medical benefits, and so that can be a challenge, especially if a patient’s disease is very aggressive. If they have progressed on ibrutinib it would be really important to start their subsequent therapy very quickly, or it can progress to Richter transformation,” Duffy said. “The economic challenges in improving can be a barrier. As pharmacists, anything we can do to facilitate the approval process, and in the clinic, I can certainly help with the prior authorization process.”

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