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or R-FM ( n = 54 ; 32 %; p < 0.001 ). However , patients treated with R-CVP had a 43 percent higher probability of requiring salvage therapy , compared with the R-CHOP cohort ( p value not reported ).

Seventy-five deaths occurred during follow-up , most of which were a result of lymphoma progression ( n = 46 ; 61 %). Risk of death resulting from lymphoma was comparable across the three treatment cohorts ( p = 0.90 ), but the risk of death from non-lymphoma related causes was higher with R-FM ( 11.2 % at 8 years ) than R-CVP ( 1.8 %; p = 0.005 ). There were no fatal infections recorded during induction therapy or among patients who relapsed .

The study did not allow maintenance therapy , “ and we were unable to estimate the effect of prolonged use of rituximab in the comparison among study arms ,” the authors wrote of the trial ’ s limitations . The researchers also noted that since the start of the FOLL05 study , bendamustine plus rituximab ( BR ) “ has been rapidly imposed as first-choice therapy ” for this patient population . “ We believe [ both R-CHOP and BR ] represent the best available options to achieve long-lasting remission in patients with previously untreated FL ,” they wrote .

Dr . Luminari reports financial support from Roche , Celgene , Gilead , Sandoz , Janssen , and Takeda .

REFERENCE

Luminari S , Ferrari A , Manni M , et al . Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma . J Clin Oncol . 2017 November 2 . [ Epub ahead of print ] chemotherapy , during KYMRIAH treatment , and until immune recovery following treatment with KYMRIAH .

Pregnant women who have received KYMRIAH may have hypogamma - globulinemia . Assess immuno globulin levels in newborns of mothers treated with KYMRIAH .

5.8 Secondary Malignancies Patients treated with KYMRIAH may develop secondary malignancies or recurrence of their leukemia . Monitor life-long for secondary malignancies . In the event that a secondary malignancy occurs , contact Novartis Pharmaceuticals Corporation at 1-844-4KYMRIAH to obtain instructions on patient samples to collect for testing .

5.9 Effects on Ability to Drive and Use Machines Due to the potential for neurological events , including altered mental status or seizures , patients receiving KYMRIAH are at risk for altered or decreased consciousness or coordination in the 8 weeks following KYMRIAH infusion . Advise patients to refrain from driving and engaging in hazardous occupations or activities , such as operating heavy or potentially dangerous machinery , during this initial period .

6 ADVERSE REACTIONS Most common adverse reactions ( incidence greater than 20 %) are hypogammaglobulinemia , infections-pathogen unspecified , pyrexia , decreased appetite , headache , encephalopathy , bleeding , hypotension , tachycardia , nausea , diarrhea , vomiting , viral infectious disorders , hypoxia , fatigue , acute kidney injury , and delirium .

The following serious adverse reactions are discussed in greater detail in another section of the label :

• Cytokine Release Syndrome [ see Warnings and Precautions ( 5.1 )]

• Neurological Toxicities [ see Warnings and Precautions ( 5.2 )]

• Infections and Febrile Neutropenia [ see Warnings and Precautions ( 5.5 )]

• Prolonged Cytopenias [ see Warnings and Precautions ( 5.6 )]

• Hypogammaglobulinemia [ see Warnings and Precautions ( 5.7 )]

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice .

The safety data described in this section reflect exposure to KYMRIAH in the clinical trial ( Study 1 ) in which 68 patients with pediatric and young adult relapsed / refractory ( R / R ) B-cell ALL received CAR-positive viable T cells .

Based on a recommended dose which was weight-based , all patients received a single intravenous dose of KYMRIAH [ see Clinical Studies ( 14 )]. The most common adverse reactions were cytokine release syndrome ( 79 %), hypogammaglobulinemia ( 43 %), infections-pathogen unspecified ( 41 %), pyrexia ( 40 %), decreased appetite ( 37 %), headache ( 37 %), encephalopathy ( 34 %), hypotension ( 31 %), bleeding episodes ( 31 %), tachycardia ( 26 %), nausea ( 26 %), diarrhea ( 26 %), vomiting ( 26 %), viral infectious disorders ( 26 %), hypoxia ( 24 %), fatigue ( 22 %), acute kidney injury ( 22 %), and delirium ( 21 %).

Eleven deaths were reported for patients who received KYMRIAH , of which 2 deaths occurred within 30 days of infusion . Seven were disease-related , three were attributed to infections , and one to intra cerebral hemorrhage . Of the two deaths before Day 30 , one patient died with CRS and progressive leukemia and the second patient had resolving CRS with abdominal compartment syndrome , coagulopathy , and renal failure when an intracranial hemorrhage occurred .

The adverse reactions with greater or equal to 10 % incidence for any Grade are summarized in Table 2 .

Table 2 . Selected Adverse Reactions ( ≥ 10 %) Following Treatment with KYMRIAH ( N = 68 )

Adverse Reaction

All Grades Grades 3 or Higher (%) (%)

Cardiac disorders a

Tachycardia 26 4

Gastrointestinal disorders Nausea 26 3 Diarrhea 26 1 Vomiting 26 1 Constipation 18 0 b Abdominal pain 16 3

General disorders and administration site conditions Pyrexia 40 15 Fatigue 22 0 Face edema 10 1 Edema peripheral 10 1 Chills 10 0

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