乌鸦传媒

SAN DIEGO -- The scientific program of the American Society of Hematology (ASH) annual meeting included thousands of posters presented over a period of 3 days. A selected few on chronic lymphocytic leukemia (CLL) are summarized below.

Obesity in CLL Patients

Obesity may diminish survival in women with CLL who undergo chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR), a study from Germany found.

Among 1,247 CLL patients on different first-line regimens, median overall survival (OS) among those treated with FCR was significantly worse in obese women compared with women of normal weight (HR 3.013, 95% CI 1.345-6.752, P=0.007), according to Moritz Fürstenau, MD, of the German CLL Study Group.

The same pattern was seen with progression-free survival as well (HR 1.743, 95% CI 1.022-2.973, P=0.041).

In the overweight (but not obese) group, there was only a trend toward worse OS (HR 1.911, 95% CI 0.909-4.017, P=0.087). Weight categories were based on body mass index (BMI) and defined as the following, with underweight patients (BMI <18.5) excluded from the analysis:

• Obese: BMI ≥30
• Overweight: BMI ≥25 but <30
• Normal weight: BMI ≥18.5 but <25

While FCR is possibly on its way out in younger CLL patients, rituximab may not be. The researchers said that obesity seems to abrogate the benefit of adding rituximab, noting that the median PFS in obese women was 44.6 months with FCR and 44.4 months with chemotherapy alone. "Faster rituximab clearance and decreased elimination half-life was reported in obese patients," they noted. "This could explain the observed effect."

The association was not seen among men. The study supports similar findings related to obesity in lymphoma patients.

CLL Risk Model in Era of Targeted Agents

A clinically validated risk model using just four readily available factors can classify relapsed or refractory CLL patients into three prognostic groups with significantly different expected OS for each, and works regardless of prior treatment with ibrutinib, idelalisib (Zydelig), or venetoclax (Venclexta), researchers reported in a poster presentation here.

Led by Jacob Soumerai, MD, of Mass General Cancer Center in Boston, they looked at data on 2,475 patients with relapsed and refractory CLL from both the Mayo Clinic CLL Database and from randomized phase III trials that compared ibrutinib (HELIOS and RESONATE), idelalisib (Studies 115, 116, and 119), and venetoclax (MURANO) to chemoimmunotherapy.

Soumerai's group first conducted univariate and multivariate analyses on 28 candidate factors (clinical, laboratory, and molecular or genetic), and ultimately narrowed these down to four risk factors that were each significantly predictive of OS on multivariate analysis:

• Beta-2 microglobulin: ≥5 mg/L
• Lactate dehydrogenase: >upper limit of normal
• Hemoglobin: <110 g/L for women and <120 g/L for men
• Time from start of last therapy: <24 month

HRs remained significant and were similar for each factor individually (0.64, 0.68, 0.55, and 0.62) in a training set of 727 patients. As such, patients were assigned a score of 1 for each risk factor, with the sum determining their risk score: low (score of 0-1), intermediate (2-3), and high (4).

In the validation sets, the model proved significant for patients previously treated with each drug:

• Ibrutinib (n=242): C-statistic 0.79 (95% 0.56-0.97, P<0.0001)
• Idelalisib (n=897): C-statistic 0.71 (95% 0.59-0.81, P<0.0001)
• Venetoclax (n=389): C-statistic 0.76 (95% 0.66-0.85, P<0.01)
• Mayo database (n=220): C-statistic 0.61 (95% 0.56-0.66, P<0.001)

The model -- -- "identifies a well-defined cohort of previously treated CLL patients with an unmet clinical need," the researchers concluded, highlighting that these patients should be targeted for prospective trials.

ARQ 531 Shows Promise in Ibrutinib-Refractory CLL

Anti-tumor activity was seen with the novel, reversible Bruton tyrosine kinase (BTK) inhibitor ARQ 531 in a small group of heavily pretreated adult lymphoma and CLL patients, including those with BTK C4815 mutations of resistance to ibrutinib.

Among 20 patients with a median of six prior lines of therapy, the drug yielded one durable partial response and stable disease in 11 patients, reported Jennifer Woyach, MD, of Ohio State University's Comprehensive Cancer Center in Columbus.

The phase I dose-escalation study looked at six doses of the oral drug (5 mg to 45 mg), and is enrolling for a seventh (65 mg). Most patients were men (90%) and all but one were white. ECOG ≤2 performance status was a requirement for study entry.

CLL was the most common cohort (75%) with three follicular lymphoma and two diffuse large B-cell lymphoma patients rounding out the rest of the group. For CLL, prior exposure to a BTK inhibitor such as ibrutinib was a requirement for enrollment, and 12 of these patients had BTK C4815 mutations (eight achieved stable disease, with five having tumor reductions of >20%).

There were no dose-limiting toxicities observed, but serious adverse events (AEs) occurred in 20% of patients. All patients had an AE of some kind, with 55% having grade ≥3 AEs. Two patients discontinued treatment due to toxicity, and one patient was given a reduced dose.