This article was originally published by Targeted Oncology 

Jennifer Woyach, MD, an associate professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center–James, discusses the rationale and efficacy for the phase 1/2 trial of acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL).

Woyach explains that acalabrutinib is an inhibitor of Bruton’s kinase (BTK), and it’s a second-generation covalent inhibitor. Similar to ibrutinib (Imbruvica), it binds irreversibly to BTK, but it is more selective than ibrutinib. Ibrutinib inhibits many structurally similar proteins, while acalabrutinib inhibits less, which is important for toxicity. She thinks that some of the toxicity seen with ibrutinib are because of those alternative targets. Some of the toxicities may lessen with acalabrutinib.

In treatment-naïve and relapsed/refractory disease, the data has looked promising with this agent, according to Woyach. In 1 study with 53 months of follow-up for 99 patients with treatment-naïve CLL, about 86% of the patients were still on treatment, which she says is impressive. The event-free survival at 48 months was 90%. This is looking promising with acalabrutinib, which is similar to what has been seen with ibrutinib in this patient population. Although she says it’s difficult to compare trial to trial, it’s good to see that it looks similar to ibrutinib in this setting.

To continue reading this article on Targeted Oncology 

This article was originally published by Cancer Therapy Advisor   

Efficacy of chimeric antigen receptor (CAR) T-cell (CAR-T) therapies in chronic lymphocytic leukemia (CLL) have lagged behind the efficacy they appear to have in other hematological malignancies such as acute lymphoblastic leukemia or diffuse large B-cell lymphoma.

There’s a growing recognition that some of the CAR-T shortfalls in CLL are due to an impaired fitness of T cells in CLL patients. Some research has shown, however, that sustained remission of CLL is associated with enrichment of a less-differentiated, early-memory phenotype of T cells in the apheresis product used to make CAR-T therapies.¹ Such findings have galvanized interest in approaches to enhance this T-cell population during the immunotherapy manufacturing process as a possible route for overcoming treatment resistance.

Now, a small study in the International Journal of Cancer reported that culturing CLL patients’ T cells with the tyrosine kinase inhibitor ibrutinib — which among other effects, inhibits a pathway involved in T-cell differentiation — boosted the viability, function, and expansion of CLL patient-derived CAR T cells as well as enriching them with a less-differentiated phenotype.²

To continue reading this article on Cancer Therapy Advisor   

Dr Karen Oldfield is a PhD candidate at the Victoria University of Wellington and a Senior Clinical Research Fellow at the Medical Research Institute of New Zealand who is looking at the use of cannabis as a cancer medicine in NZ.  All information collected will be treated in a confidential manner and will not be disclosed to any other agencies. If you are interested in helping with this research, read on…

Dr Oldfield has approached CLL Advocates NZ to invite CLL patients to take part in this project:

“Medical cannabis is a topical subject.  As part of my PhD research, I am seeking NZ residents over the age of 18 with an oncology/cancer diagnosis to take part in a 5-10 minute online survey about their thoughts about the use of cannabis as medicine.  For further information, you can find the participant information sheet here https://is.gd/OncInfo2 . If you are keen to take part, please find the survey at the following link: https://is.gd/OncPatientQ. Thanks for taking the time to consider participating in this research!”

We encourage you to help with this valuable study.

This article was originally published by Cancer Therapy Advisor   

Chronic lymphocytic leukemia (CLL) is well known for its close relationship with immune dysfunction, with around a third of patient deaths attributable to bacterial or viral infections. And while the relative risk of death due to the malignancy itself has declined over the past few decades, the risk of death from infection among those with CLL has remained constant, some research suggests.¹

Infections often precede a formal diagnosis of CLL. Patients are known to suffer severe infections such as pneumonia up to 10 years prior to being diagnosed. Such findings pose a chicken-or-egg conundrum: Does the immune dysfunction occur prior to the development of CLL, potentially driving the development of the malignancy, or do CLL cells arise first, causing immune dysfunction long before the disease is diagnosed?

Shedding fresh light on this question, a group of Danish researchers undertook a retrospective analysis of nationwide Danish cancer registries and examined CLL patients’ history of antimicrobial use as a proxy for infection susceptibility. In line with previous studies, the researchers found that antimicrobial use began to rise 6 years prior to CLL diagnosis.

But even before then, patients with leukemia had used more macrolides, antimycotics, and antivirals than healthy controls for up to 22 years before they were diagnosed. The authors wrote that this time window jibes well with the theory that immune dysfunction, and/or infections, develop prior to CLL and could potentially play a causal role in driving the disease. The findings were published last month in Leukemia.²

To continue reading this article on Cancer Therapy Advisor   

This article was originally published by Targeted Oncology

During a virtual Case Based Peer Perspectives event, Jan A. Burger, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, TX, discussed testing and the treatment options for chronic lymphocytic leukemia (CLL), based on the a case of 71-year-old female patient.

Targeted Oncology^TM: What testing would you order to confirm diagnosis if you saw this patient in the clinic?

BURGER: We need to establish the diagnosis by flow cytometry and then we would do, at a minimum, FISH cytogenetics and, ideally, the mutational status. Cytogenetics can change, but
mutational status usually doesn’t change. If that’s been established somewhere outside [of your clinic], then you don’t have to repeat that test.

It’s important to repeat cytogenetics if you talk about the relapse setting. But here, we’re treating in the frontline setting, and she was tested. She was found to be IGHV unmutated and [positive
for] del(11q). That, traditionally, has been regarded as a higher-risk disease status because these patients respond OK to standard chemotherapy, but they have short remissions and survival times with FCR [fludarabine, cyclophosphamide, and rituximab (Rituxan)], BR [bendamustine plus rituximab], and those kinds of regimens compared with low-risk patients, such as those [who are positive for] deletion 13q and have IGHV mutated disease.

In terms of these sequences, when you see a patient with lymphocytosis, you send for flow cytometry, and part of the flow cytometry panel can test for additional markers, CD38 and ZAP-70. We have it [at MD Anderson], but I’m not sure if there are any outside routine flow cytometry labs reporting CD38 positivity or negativity or ZAP-70. These markers used to be very popular 10
years or so ago when IGHV-mutation status was not so commonly done and was more complicated to get. Nowadays, there’s a shift with sending a sample directly for IGHV-mutation testing.

To continue reading this article here on Targeted Oncology

This article was originally published by Targeted Oncology

During a virtual Case Based Peer Perspectives event, Steven Coutre, MD, professor of Medicine (Hematology), Standford University Medical Center, reviewed a case of a 53-year-old woman who first presented with elevated white blood cell count. The patient was later diagnosed with chronic lymphocytic leukemia (CLL).

Targeted Oncology™: What are your initial impressions of this case?

COUTRE: I think we’d all agree that this is a patient who requires observation at this point. Clinically, this patient is at Rai stage 0. That 1 × 1 cm [lymph node] doesn’t qualify as lymphadenopathy. It certainly doesn’t need a CT scan or a bone marrow, and we can choose whether to do mutation analysis or FISH, but those results are not going to change the management approach.

To establish a diagnosis, flow cytometry was carried out showing the typical immunophenotype. Additional testing was conducted, showing the patient has no cytogenetic abnormality by FISH. Unfortunately, the patient had a bone marrow done, and it showed evidence of CLL. She was observed and did fine for 5 years, and she’s still quite young. Her WBC count has more than doubled, she’s significantly anemic, her platelet count has gone down, and the lymphadenopathy is 4 cm × 3

What are the treatment options for this patient?

The RESONATE trial [NCT01578707] evaluated patients who were previously treated for CLL and SLL [small lymphocytic leukemia] and who were randomized to receive ibrutinib [Imbruvica] at 420 mg once daily versus IV ofatumumab [Arzerra] at an initial dose of 300 mg, followed by 2000 mg for 11 doses over 24 weeks.¹

It’s no big surprise how well ibrutinib did compared with ofatumumab. The differences were highly significant. The most recent data involving 6-year follow-up published last year in Blood show that the median PFS [progression-free survival] is still not reached. These patients who entered this trial were not your average patients. The patient in our case would not have been eligible for the trial. Having a 4-year response to FCR would not [have met eligibility] for this trial. These were much worse relapsed patients, and yet here we are in 2020, and the median PFS has still not been reached with ibrutinib in this trial versus 8.11 months for the ofatumumab arm [HR, 0.133; 95% CI, 0.099-0.178].

To continue reading this article here on Targeted Oncology