How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report

Background: The t (2; 5) chromosomal rearrangement of the ALK gene with nucleophosmin 1 gene (NPM1), resulting in an NPM1–ALK fusion, was first demonstrated in 1994 in anaplastic large cell lymphoma, (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and the monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK+, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of brentuximab, still pending allo-SCT after two failed donor selections. Facing a new therapeutic failure, we requested and obtained authorization from the Italian drug regulatory agency to administer 250 mg of crizotinib twice a day, a drug incomprehensibly not registered for ALCL ALK +. Conclusions: The response to crizotinib was optimal since no adverse event occurred, and CT-PET scans persisted negative; this drug has proved to be a valid bridge to allo-SCT.

How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas Alk+ Therapy: A Case Report

Background: The t (2; 5) chromosomal rearrangement and resulting nucleophosmin (NPM1) -ALK fusion was first observed in 1994 in anaplastic large cell lymphoma (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab-vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK +, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of Brentuximab, still pending allo-SCT after two failed donor selection. Facing of a new therapeutic failure, we requested the Italian drug regulatory agency, and obtained the authorization, to administer 250 mg twice a day of Crizotinib, a drug incomprehensibly not registered for ALCL ALK +. Conclusions: The response to Crizotinib was optimal, since no adverse event occurred, and CT-PET persisted negative; this drug has proved to be a valid bridge to allo-SCT

EULAR recommendations for the management of large vessel vasculitis

Objectives:To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis.Methods:An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion.Results:Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures.Conclusions:On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

EULAR recommendations for the management of primary small and medium vessel vasculitis

Objectives:To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis.Methods:An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion.Results:In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures.Conclusions:On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Satisfaction with Pharmacotherapy for Approved and Off-Label Indications—A Delphi Study

BACKGROUND: Prescribing for non-approved uses is widespread in the treatment of AIDS, cancer, and pediatric illnesses, but it is by no means limited to these areas. Few studies have been performed evaluating reasons for off-label prescribing. OBJECTIVE: To explore the satisfaction with drug therapy as one of the potential reasons for off-label uses by testing a hypothesis that the satisfaction with drug therapy for off-label indications is lower than for approved indications. METHODS: The study compared the satisfaction with drug therapy for known off-label indications with a control group of approved indications. Twenty-four of the first 50 single-ingredient drugs, according to their share in the drug cost budget of the Slovenian Compulsory Health Insurance, had 86 different off-label indications eligible for inclusion. A control group of 86 approved indications was randomly selected from the list of all possible approved indications for the same 24 drugs. A 2–round Delphi technique, involving an expert panel of physicians who are members of the drug regulatory agency, was used to evaluate the satisfaction with drug therapy for selected indications. RESULTS: After the second round of the Delphi study, the median scores of satisfaction with drug therapy for approved and off-label indications were 7.00 and 6.50, respectively (p = 0.001). CONCLUSIONS: The study shows that the satisfaction with available drug therapy for off-label indications is lower than for approved indications. The statistical association, biologic plausibility, and coherence with existing information, as well as the temporality of the association, provide supporting evidence that low satisfaction with drug therapy is one of the incentives for off-label use.