“A new survey of hospitals and academic medical centers finds that a recent move by Genentech to switch distribution of three widely used cancer treatments – Avastin, Rituxan and Herceptin – is resulting in higher costs, reduced access to the medications and delays in treating patients. And the institutions are hoping the results will prompt the drug maker, which says it’s unaware of such problems, to revert to its earlier distribution program.
“Here’s the background: Last fall, Genentech began using just a few distributors that specialize in handling such medicines. Until then, the Roche unit used dozens of wholesalers, although the specialty distributors are actually divisions of some of those same wholesalers. Genentech says the change was made to save money, but also make distribution more efficient and prevent the possibility of shortages.
“However, most of the institutions – 93% – say they had not experienced shortages, and the move has disrupted not only their finances, but patient care. The survey also found that 81% say the switch will have a moderate to significant impact on their expenses. Meanwhile, 63% say deliveries have been unreliable and 88% reported a delay in patient treatment because one of the drugs was unavailable.
“The institutions say they are forced to increase inventories to hedge against any supply disruptions that may occur because shipping can take longer, depending upon the location of the distributor. Some institutions say they cannot afford to keep large amounts of drug on hand, which can result in delays in treating new patients or unexpected events. And previous discounts may no longer be available.”
Editor’s note: This article discusses the results of a clinical trial—a research study with volunteer patients. The goal of the trial is to test a new treatment for high-risk chronic lymphocytic leukemia (CLL). The treatment combines two drugs, ibrutinib and rituximab. Patients participating in the trial have had promising responses to the treatment. Further studies will continue to evaluate the new treatment.
“Patients with high-risk chronic lymphocytic leukemia demonstrated encouraging rates of objective response and durable remission after treatment with ibrutinib plus rituximab, according to results of a single-center phase 2 study.
“Jan A. Burger, MD, PhD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues assessed the activity and safety of ibrutinib (Imbruvica; Pharmacyclics, Janssen), a Bruton’s tyrosine kinase inhibitor, in combination with the chimeric monoclonal antibody rituximab (Rituxan; Genentech, Biogen Idec) in 40 adults with high-risk CLL.
“All patients either experienced short PFS — defined as less than 36 months — after first-line chemoimmunotherapy, or they demonstrated high-risk cytogenetic abnormalities, such as deletion 17p, deletion 11q or TP53 mutation…
“ ‘From this study, can we state that the time for ibrutinib monotherapy is over, and that combination with anti-CD20 antibodies the preferential treatment partner, as is the case for idelalisib (Zydelig, Gilead)?’ Ghia wrote. ‘Despite [these] promising results, we will probably need to wait. Short follow-up of only 18 months makes it difficult to ascertain whether an actual benefit in PFS or OS exists when compared with the monotherapy regimen. The clinical advantage of adding a second drug (rituximab) needs to be consistently proven because of the relevant economic consequences: The additional cost of combinations might jeopardize the overall sustainability of future treatments.’ ”
“Vitamin D deficiency (VDD) contributes to worse outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, according to a study published online Aug. 18 in the Journal of Clinical Oncology.
“Jörg Thomas Bittenbring, MD, from Universitätsklinikum des Saarlandes in Germany, and colleagues examined the impact and mechanisms of VDD in patients with DLBCL. Chemoluminescent immunoassays were used to evaluate 359 pretreatment 25-hydroxyvitamin D3 serum levels from the RICOVER-60 study (6 Versus 8 Cycles of Biweekly CHOP-14 With or Without Rituximab) and 63 from the RICOVER-noRTh study (an amendment to the RICOVER-60 study).
“The researchers found that RICOVER-60 patients treated with rituximab with VDD (≤8 ng/mL) had 3-year event-free survival (EFS) of 59% and 3-year overall survival (OS) of 70%, while those with vitamin D levels >8 ng/mL treated with rituximab had EFS and OS of 79 and 82%, respectively. In multivariate analysis adjusting for International Prognostic Index risk factors, these differences remained significant, with hazard ratios of 2.1 (P = 0.008) for EFS and 1.9 (P = 0.040) for OS. In all 7 individuals with VDD, there were significant increases in rituximab-mediated cellular cytotoxicity (RMCC; P < 0.001) after substitution and normalization of their vitamin D levels.”
“The U.S. Food and Drug Administration today approved Zydelig (idelalisib) to treat patients with three types of blood cancers.
“Zydelig is being granted traditional approval to treat patients whose chronic lymphocytic leukemia (CLL) has returned (relapsed). Used in combination with Rituxan (rituximab), Zydelig is to be used in patients for whom Rituxan alone would be considered appropriate therapy due to other existing medical conditions (co-morbidities). Zydelig is the fifth new drug with breakthrough therapy designation to be approved by the FDA and the third drug with this designation approved to treat CLL.
“The FDA is also granting Zydelig accelerated approval to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), another type of non-Hodgkin lymphoma. Zydelig is intended to be used in patients who have received at least two prior systemic therapies.
“ ‘In less than a year, we have seen considerable progress in the availability of treatments for chronic lymphocytic leukemia,’ said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. ‘Zydelig’s approval to treat CLL reflects the promise of the breakthrough therapy designation program and represents the FDA’s commitment to working cooperatively with companies to expedite a drug’s development, review and approval.’ ”
“A novel immune-based combination therapy for the initial treatment of chronic lymphocytic leukemia (CLL) does not appear to improve on results achieved with established regimens that include chemotherapy.
“In a phase 2 study, investigators combined rituximab (Rituxan, MabThera and Roche), the monoclonal antibody widely used for CLL, and lenalidomide (Revlimid, Celgene), an immunomodulatory agent that is not approved in these patients.
“The idea behind the pairing was to avoid chemotherapy, which is generally not well tolerated by older or infirm CLL patients and is part of all regimens containing rituximab, say the investigators, led by Danelle James, MD, from the Moores Cancer Center at the University of California, San Diego.”
Editor’s note: A potential alternative to chemotherapy for chronic lymphocytic leukemia (CLL) was tested in volunteer patients, but did not show improved results over chemo. The treatment combines the drug Rituxan with another drug called Revlimid, which is meant to boost a patient’s immune system to help fight cancer. Researchers hope to test other combinations of non-chemo drugs to see if they will prove more successful.
“In a UK phase II study reported in the Journal of Clinical Oncology, Hillmen et al assessed the safety and activity of adding rituximab (Rituxan) to chlorambucil (Leukeran) in first-line treatment of chronic lymphocytic leukemia (CLL). Such a regimen may be an alternative to fludarabine-based treatment or chlorambucil monotherapy in elderly patients and those with comorbidities.
“In the study, 100 patients in 12 UK centers received first-line rituximab (375 mg/m2 on day 1 of cycle 1 and 500 mg/m2 thereafter) plus chlorambucil (10 mg/m2 on days 1–7) for six 28-day cycles. Patients responding but not achieving complete response could receive an additional six cycles of chlorambucil alone.
“Patients had a median age of 70 years (range, 43–86 years) and a median of seven comorbidities, 66% were male, 56% had Binet stage C disease, 36% had IgVH mutation, and 13q deletion, 12q trisomy, 11q deletion, and 17p deletion were present in 43%, 16%, 13%, and 3%, respectively.”
Editor’s note: A new clinical trial with volunteer patients tested a treatment that combines the drug chlorambucil (Leukeran) with the drug rituximab (Rituxan). The treatment was found to be safe, and may be more effective than treatment with chlorambucil alone. This combination treatment might be a good option for people with chronic lymphocytic leukemia (CLL) who might not be able to take fludarabine-based treatment, especially elderly patients and patients with comorbidities (two or more diseases).