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Heard in the Blogosphere

Medicare Part B Payment Caps Will Limit Outpatient Access to CAR T-Cell Therapy
“[ Recent ] proposals would limit Medicare reimbursement when [ CAR T-cell therapy ] is administered in outpatient settings ... to the average sales price of the therapy plus an amount capped at $ 1,000 for most drugs and up to $ 2,000 for immunotherapies like CAR T-cell therapy .
But the initial investments required to furnish CAR T-cell therapy in outpatient settings greatly exceed $ 1,000 to $ 2,000 per patient . Consequently , many practices are facing insurmountable economic barriers to administering CAR T-cell therapy therapies if they cannot recoup the financial risks and expenses .
Long before giving a CAR T-cell infusion to the first patient , putting a program in place requires considerable outlays to recruit , train , and prepare staff ; to expand the facility ; and to establish contracts with other providers and manufacturers . Unless Medicare underwrites these upfront investment costs and the ongoing costs of running a CAR T-cell therapy program , many centers will decide not to adopt this therapy .
Changing the reimbursement policy may thus paradoxically limit access to CAR T-cell therapy among people covered by Medicare , the population in which cancers are most often identified .
Any changes to Part B reimbursement must balance policy concerns about financial incentives while also preserving — and expanding — access to novel , transformative treatments like CAR T-cell therapy in the outpatient setting .”
— Richard Maziarz , MD , hematologist , professor of medicine , and director of the Blood and Marrow Transplant and Cellular Therapy Program at Oregon Health and
Science University , and Sophie Snyder , managing director at Qualia Bio , in STAT
Brief Summary of Prescribing Information for IMBRUVICA ® ( ibrutinib ) IMBRUVICA ® ( ibrutinib ) capsules , for oral use IMBRUVICA ® ( ibrutinib ) tablets , for oral use
INDICATIONS AND USAGE Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma : IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia ( CLL )/ small lymphocytic lymphoma ( SLL ). Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma with 17p deletion : IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia ( CLL )/ small lymphocytic lymphoma ( SLL ) with 17p deletion .
CONTRAINDICATIONS None
WARNINGS AND PRECAUTIONS Hemorrhage : Fatal bleeding events have occurred in patients who received IMBRUVICA . Major hemorrhage ( ≥ Grade 3 , serious , or any central nervous system events ; e . g ., intracranial hemorrhage [ including subdural hematoma ], gastrointestinal bleeding , hematuria , and post procedural hemorrhage ) occurred in 4 % of patients , with fatalities occurring in 0.4 % of 2,838 patients who received IMBRUVICA in 27 clinical trials . Bleeding events of any grade including bruising and petechiae occurred in 39 %, and excluding bruising and petechiae occurred in 23 % of patients who received IMBRUVICA , respectively . The mechanism for the bleeding events is not well understood . Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA increases the risk of major hemorrhage . Across clinical trials , 3.1 % of 2,838 patients who received IMBRUVICA without antiplatelet or anticoagulant therapy experienced major hemorrhage . The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4 %, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1 %. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA . Monitor for signs and symptoms of bleeding . Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding [ see Clinical Studies ( 14 ) in Full Prescribing Information ]. Infections : Fatal and non-fatal infections ( including bacterial , viral , or fungal ) have occurred with IMBRUVICA therapy . Grade 3 or greater infections occurred in 21 % of 1,476 patients who received IMBRUVICA in clinical trials [ see Adverse Reactions ]. Cases of progressive multifocal leukoencephalopathy ( PML ) and Pneumocystis jirovecii pneumonia ( PJP ) have occurred in patients treated with IMBRUVICA . Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections . Monitor and evaluate patients for fever and infections and treat appropriately . Cytopenias : In 645 patients with B-cell malignancies who received IMBRUVICA as a single agent , grade 3 or 4 neutropenia occurred in 23 % of patients , grade 3 or 4 thrombocytopenia in 8 % and grade 3 or 4 anemia in 3 %, based on laboratory measurements . Monitor complete blood counts monthly . Cardiac Arrhythmias and Cardiac Failure : Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA . Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2 % of patients , Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4 %, and Grade 3 or greater cardiac failure occurred in 1 % of 1,476 patients who received IMBRUVICA in clinical trials . These events have occurred particularly in patients with cardiac risk factors , hypertension , acute infections , and a previous history of cardiac arrhythmias [ see Adverse Reactions ]. At baseline and then periodically , monitor patients clinically for cardiac arrhythmias and cardiac failure . Obtain an ECG for patients who develop arrhythmic symptoms ( e . g ., palpitations , lightheadedness , syncope , chest pain ) or new onset dyspnea . Manage cardiac arrhythmias and cardiac failure appropriately , and if it persists , consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines [ see Dosage and Administration ( 2.2 ) in Full Prescribing Information ]. Hypertension : Hypertension occurred in 19 % of 1,476 patients who received IMBRUVICA in clinical trials . Grade 3 or greater hypertension occurred in 8 % of patients . Based on data from 1,124 of these patients , the median time to onset was 5.9 months ( range , 0.03 to 24 months ). Monitor blood pressure in patients treated with IMBRUVICA and initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA as appropriate . Second Primary Malignancies : Other malignancies ( 10 %), including nonskin carcinomas ( 4 %), occurred among the 1,476 patients who received IMBRUVICA in clinical trials . The most frequent second primary malignancy was non-melanoma skin cancer ( 6 %).
IMBRUVICA ® ( ibrutinib )
Tumor Lysis Syndrome : Tumor lysis syndrome has been infrequently reported with IMBRUVICA . Assess the baseline risk ( e . g ., high tumor burden ) and take appropriate precautions . Monitor patients closely and treat as appropriate . Embryo-Fetal Toxicity : Based on findings in animals , IMBRUVICA can cause fetal harm when administered to a pregnant woman . Administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 2-20 times higher than those reported in patients with hematologic malignancies . Advise pregnant women of the potential risk to a fetus . Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month after the last dose . [ see Use in Specific Populations ].
ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling :
• Hemorrhage [ see Warnings and Precautions ]
• Infections [ see Warnings and Precautions ]
• Cytopenias [ see Warnings and Precautions ]
• Cardiac Arrhythmias and Cardiac Failure [ see Warnings and Precautions ]
• Hypertension [ see Warnings and Precautions ]
• Second Primary Malignancies [ see Warnings and Precautions ]
• Tumor Lysis Syndrome [ see Warnings and Precautions ]
Clinical Trials Experience : Because clinical trials are conducted under widely variable conditions , adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice .
The data in the WARNINGS AND PRECAUTIONS reflect exposure to IMBRUVICA in 6 trials as a single agent at 420 mg orally once daily in 475 patients and at 560 mg orally once daily in 174 patients and in 4 trials administered in combination with other drugs at 420 mg orally once daily in 827 patients . Among these 1,476 patients with B-cell malignancies who received IMBRUVICA , 87 % were exposed for 6 months or longer and 68 % were exposed for greater than one year . In this pooled safety population of 1,476 patients with B-cell malignancies , the most common adverse reactions ( ≥30 %) were thrombocytopenia , diarrhea , fatigue , musculoskeletal pain , neutropenia , rash , anemia , and bruising .
Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma : The data described below reflect exposure to IMBRUVICA in one single-arm , openlabel clinical trial ( Study 1102 ) and five randomized controlled clinical trials ( RESONATE , RESONATE-2 , HELIOS , iLLUMINATE , and E1912 ) in patients with CLL / SLL ( n = 2,016 total , including n = 1,133 patients exposed to IMBRUVICA ). In general , patients with creatinine clearance ( CLcr ) ≤ 30 mL / min , AST or ALT ≥ 2.5 x ULN , or total bilirubin ≥ 1.5x ULN ( unless of non-hepatic origin ) were excluded from these trials . In Study E1912 , patients with AST or ALT > 3 x ULN or total bilirubin > 2.5 x ULN were excluded . Study 1102 included 51 patients with previously treated CLL / SLL . RESONATE included 386 randomized patients with previously treated CLL or SLL who received single agent IMBRUVICA or ofatumumab . RESONATE-2 included 267 randomized patients with treatment naïve CLL or SLL who were 65 years or older and received single agent IMBRUVICA or chlorambucil . HELIOS included 574 randomized patients with previously treated CLL or SLL who received IMBRUVICA in combination with BR or placebo in combination with BR . iLLUMINATE included 228 randomized patients with treatment naïve CLL / SLL who were 65 years or older or with coexisting medical conditions and received IMBRUVICA in combination with obinutuzumab or chlorambucil in combination with obinutuzumab . E1912 included 510 patients with previously untreated CLL / SLL who were 70 years or younger and received IMBRUVICA in combination with rituximab or received fludarabine , cyclophosphamide , and rituximab ( FCR ).
The most common adverse reactions in patients with CLL / SLL receiving IMBRUVICA ( ≥ 30 %) were thrombocytopenia , diarrhea , fatigue , musculoskeletal pain , neutropenia , rash , anemia , bruising , and nausea .
Four to 10 percent of patients with CLL / SLL receiving IMBRUVICA discontinued treatment due to adverse reactions . These included pneumonia , hemorrhage , atrial fibrillation , neutropenia , arthralgia , rash , and thrombocytopenia . Adverse reactions leading to dose reduction occurred in approximately 9 % of patients .
Study 1102 : Adverse reactions and laboratory abnormalities from Study 1102 ( N = 51 ) using single agent IMBRUVICA 420 mg daily in patients with previously treated CLL / SLL occurring at a rate of ≥ 10 % with a median duration of treatment of 15.6 months are presented in Tables 1 and 2 .