For:
BRAF+ Advanced Melanoma or BRAF+ Melanoma Involving Lymph Nodes After Surgery
Important Safety Information

New Primary Malignancies. Cutaneous Malignancies: Across clinical trials of TAFINLAR administered with MEKINIST (“the combination”), the incidence of cutaneous squamous cell carcinomas (cuSCCs), in...

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Indications TAFINLAR, in combination with MEKINIST, is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.

TAFINLAR, in combination with MEKINIST, is indicated for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.

Limitation of Use: TAFINLAR is not indicated for the treatment of patients with wild-type BRAF melanoma.

Efficacy—Metastatic

Study Designs

COMBI-v

COMBI-v was a phase 3, multicenter, open-label, randomized (1:1), active-controlled trial of 704 patients with unresectable (stage IIIC) or metastatic (stage IV) BRAF V600E/K mutation–positive cutaneous melanoma. Patients were randomized to receive TAFINLAR 150 mg twice daily + MEKINIST 2 mg once daily (n=352) or single-agent vemurafenib 960 mg twice daily (n=352). Treatment was continued until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and safety.1-3

 

COMBI-d

COMBI-d was a phase 3, multicenter, double-blind, randomized (1:1), active-controlled trial of 423 patients with unresectable (stage IIIC) or metastatic (stage IV) BRAF V600E/K mutation–positive cutaneous melanoma. Patients were randomized to receive TAFINLAR 150 mg twice daily + MEKINIST 2 mg once daily (n=211) or TAFINLAR 150 mg twice daily + placebo (n=212). Treatment was continued until disease progression or unacceptable toxicity. The primary end point was PFS. Secondary end points included OS, DOR, ORR, and safety. At the time of the primary analysis (August 2013), patients taking TAFINLAR + MEKINIST were progression free for a median of 9.3 months (95% CI, 7.7-11.1) vs 8.8 months (95% CI, 5.9-10.9) with TAFINLAR + matching placebo (hazard ratio [HR], 0.75; 95% CI, 0.57-0.99; P=.035).2-4

 

Pooled COMBI-d/v

Pooled analysis of COMBI-d and COMBI-v consisted of 563 first-line patients with BRAF V600E/K mutation–positive unresectable or metastatic melanoma. All patients in the analysis received TAFINLAR 150 mg twice daily + MEKINIST 2 mg once daily in either COMBI-d (data cutoff, December 10, 2018) or COMBI-v (data cutoff, October 8, 2018). Median follow-up was 22 months (range, 0-76).5,6

 

BRF113220

BRF113220 was an open-label phase 1 and 2 study of patients with unresectable stage IIIC or IV BRAF V600E/K mutation–positive melanoma. This study had 4 parts (A, B, C, D). Analysis here only includes patients enrolled in Part C. Patients were randomly assigned 1:1:1 to receive either TAFINLAR 150 mg twice daily + MEKINIST 2 mg once daily, TAFINLAR 150 mg twice daily + MEKINIST 1 mg once daily, or TAFINLAR 150 mg monotherapy twice daily. Patients who progressed in the TAFINLAR monotherapy arm were allowed to cross over to the TAFINLAR 150-mg twice daily + MEKINIST 2-mg once daily arm. Efficacy and safety were analyzed at 4 and 5 years. End points included treatment response, DOR, PFS, OS, and safety.7

 

COMBI-MB

COMBI-MB was a phase 2, nonrandomized, open-label, multicenter, multicohort trial of 121 patients with BRAF V600E/K mutation–positive melanoma and at least 1 measurable intracranial lesion. Patients received TAFINLAR 150 mg twice daily + MEKINIST 2 mg once daily. Treatment was continued until disease progression or unacceptable toxicity. The primary end point was intracranial response rate, defined as the percentage of patients with a confirmed intracranial response per Response Evaluation Criteria In Solid Tumors v1.1, modified to allow up to 5 intracranial target lesions at least 5 mm in diameter, as assessed by independent review.2,3,8

5-Year Overall Survival and Progression-Free Survival—COMBI-v

In COMBI-v–For the first-line treatment of patients with BRAF V600E/K unresectable or metastatic melanoma

36% OF PATIENTS ALIVE AT 5 YEARS5

Overall survival in COMBI-v5

TAFINLAR + MEKINIST 5-year Overall Survival COMBI-V
  • At the interim analysis (April 2014), the median OS was not reached for patients taking TAFINLAR + MEKINIST vs 17.2 months for vemurafenib9
    Risk of mortality reduced by 31% (HR, 0.69; 95% CI, 0.53-0.89; P=.005)
     
  • Crossover was permitted after an interim OS analysis demonstrating significant benefit in COMBI-v5*
  • Results at 5 years were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error

*COMBI-v was stopped early by the Independent Data Monitoring Committee after the preplanned interim analysis (222 events; 32%) conducted in April 2014 showed OS results that crossed the prespecified efficacy stopping boundary (P<.0214), at which point the interim analysis became final. Patients will continue to be followed until death, withdrawal of consent, loss to follow-up, or have had at least 5 years of follow-up.1,9,10

OS is one of the most important measures of efficacy in metastatic melanoma; TAFINLAR + MEKINIST has high OS rates at 4 and 5 years in a phase 3 trial
44% REDUCTION IN RISK OF PROGRESSION AT PREPLANNED INTERIM ANALYSIS9

Progression-free survival analysis of the intention-to-treat population in COMBI-v5

TAFINLAR® (dabrafenib) + MEKINIST® (trametinib) progression-free survival analysis

 

20% of patients living progression free at 5 years5

  • In the interim analysis, median PFS was 11.4 months (95% CI, 9.9-14.9) for TAFINLAR + MEKINIST and 7.3 months (95% CI, 5.8-7.8) for vemurafenib (HR, 0.56; 95% CI, 0.46-0.69; P<.001)2
  • Results at 5 years were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error
TAFINLAR + MEKINIST continues to be the most prescribed combination targeted therapy for patients with BRAF+ Melanoma WORLDWIDE as of December 2021

5-Year Response Rates–Pooled COMBI-d/v Analysis

In the pooled analysis of COMBI-d and COMBI-v–For the first-line treatment of patients with BRAF V600E/K unresectable or metastatic melanoma

DEPTH OF RESPONSE THAT LASTS5,6

TAFINLAR + MEKINIST 5-year pooled analysis data

CR, complete response; DCR, disease control rate.
aDCR is defined as CR + partial response + stable disease (SD); SD is not a component of overall response rate and can reflect the natural progression of disease rather than a direct therapeutic effect.
bTwo patients are excluded from this analysis because they had no measurable disease at baseline.5

  • In the primary analysis for COMBI-d, complete response (CR) for patients taking TAFINLAR + MEKINIST was 10%, partial response (PR) was 56%, and stable disease (SD) was 26%, for a total disease control rate (DCR) of 92%. For patients taking TAFINLAR monotherapy, CR was 9%, PR was 43%, and SD was 33%, for a total DCR of 84%4
  • In the interim analysis for COMBI-v, CR for patients taking TAFINLAR + MEKINIST was 13%, PR was 51%, and SD was 26%, for a total DCR of 91%. For patients taking vemurafenib, CR was 8%, PR was 44%, and SD was 30%, for a total DCR of 82%9
  • Results at 5 years were not prespecified and are observational in nature; as such, there was no prespecified statistical procedure controlling for type 1 error
Efficacy proven in a larger phase 3 trial patient population than any other combination targeted therapy

Efficacy in Patients With Brain Metastases

In COMBI-MB–For the first-line treatment of patients with BRAF V600E/K unresectable or metastatic melanoma

50% OF PATIENTS WITH BRAIN METASTASES HAD AN INTRACRANIAL RESPONSE2,3

TAFINLAR + MEKINIST efficacy in patients with brain metastases

Clinical results from the COMBI-MB trial

  • The median duration of intracranial response was 6.4 months (range, 1-31 months)2,3
  • In Cohort A (n=76) among patients with asymptomatic brain metastasis who did not receive previous local brain therapy and had Eastern Cooperative Oncology Group performance status of 1 or 0, intracranial response was 58% (95% CI, 46%-69%)8
TAFINLAR + MEKINIST is the only targeted therapy recommended by ASCO guidelines for the treatment of brain metastases in patients with BRAF+ melanoma

ASCO, American Society of Clinical Oncology.

Time to Response

In BRF113220–For the first-line treatment of patients with BRAF V600E/K unresectable or metastatic melanoma

50% OF PATIENTS WHO RESPONDED ALREADY ACHIEVED A RESPONSE BY 1.8 MONTHS7

In a phase 1 and 2, open-label study of TAFINLAR + MEKINIST in patients with unresectable stage IIIC or IV BRAF V600E/K–mutant metastatic melanoma7

Among patients who responded (n=97) MEDIAN TIME TO RESPONSE 1.8 months
  • The primary end point was PFS; PFS in the TAFINLAR + MEKINIST group at 48 and 60 months was 13% (95% CI, 5%-25%) vs 3% (95% CI, 0%-11%) for TAFINLAR alone (HR, 0.44; 95% CI, 0.28-0.67)7†

There were no prespecified formal statistical tests for comparing the results of treatment with the combination of TAFINLAR + MEKINIST with treatment with TAFINLAR monotherapy for the efficacy end points, including end points of ORR, PFS, and OS. Therefore, no conclusions or statistical inferences can be drawn from this study.

Give your patients with metastatic melanoma the chance for a rapid response

References: 1. Supplement to: Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-39. 2. Tafinlar [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 3. Mekinist [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 4. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877-1888. 5. Supplement to: Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381(7):626-636. 6. Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381(7):626-636. 7. Long GV, Eroglu Z, Infante J, et al. Long-term outcomes in patients with BRAF V600–mutant metastatic melanoma who received dabrafenib combined with trametinib. J Clin Oncol. 2018;36(7):667-673. 8. Davies MA, Saiag P, Robert C, et al. Dabrafenib plus trametinib in patients with BRAF V600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017;18(7):863-873. 9. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-39. 10. Data on file. Clinical study report. MEK116513. Novartis Pharmaceuticals Corp; January 15, 2015. 11. Data on file. BRAF inhibitors – worldwide numbers. RITM2438789. Novartis Pharmaceuticals Corp, 2022. 12. Zelboraf [prescribing information]. South San Francisco, CA: Genentech Inc; 2020. 13. Cotellic [prescribing information]. South San Francisco, CA: Genentech Inc; 2018. 14. Braftovi [prescribing information]. Boulder, CO: Array BioPharma Inc; 2020. 15. Mektovi [prescribing information]. Boulder, CO: Array BioPharma Inc; 2020. 16. Vogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO Guideline. J Clin Oncol. 2022;40(5):492-516.

Indications

TAFINLAR, in combination with MEKINIST, is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.

TAFINLAR, in combination with MEKINIST, is indicated for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.

Limitation of Use: TAFINLAR is not indicated for the treatment of patients with wild-type BRAF melanoma.

Important Safety Information

New Primary Malignancies.

Cutaneous Malignancies

Across clinical trials of TAFINLAR administered with MEKINIST (“the combination”), the incidence of cutaneous squamous cell carcinomas (cuSCCs), including keratoacanthomas, occurred in 2% of patients. Basal cell carcinoma and new primary melanoma occurred in 3% and <1% of patients, respectively. 

Perform dermatologic evaluations prior to initiation of the combination, every 2 months while on therapy, and for up to 6 months following discontinuation.

Noncutaneous Malignancies

Based on its mechanism of action, TAFINLAR may promote the growth and development of malignancies with activation of monomeric G protein (RAS) through mutation or other mechanisms. Across clinical trials of TAFINLAR monotherapy and the combination, noncutaneous malignancies occurred in 1% of patients.

Monitor patients receiving the combination for signs or symptoms of noncutaneous malignancies. Permanently discontinue TAFINLAR for RAS-mutation–positive noncutaneous malignancies. No dose modification is required for MEKINIST in patients who develop noncutaneous malignancies.

Tumor Promotion in BRAF Wild-type Tumors. In vitro experiments have demonstrated paradoxical activation of mitogen-activated protein kinase (MAPK) signaling and increased cell proliferation in BRAF wild-type cells that are exposed to BRAF inhibitors. Confirm evidence of BRAF V600E or V600K mutation status prior to initiation of therapy.

Hemorrhage. Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur with the combination. Fatal cases have been reported.

Across clinical trials of the combination, hemorrhagic events occurred in 17% of patients. Gastrointestinal hemorrhage occurred in 3% of patients who received the combination. Intracranial hemorrhage occurred in 0.6% of patients who received the combination. Fatal hemorrhage occurred in 0.5% of patients who received the combination. The fatal events were cerebral hemorrhage and brainstem hemorrhage.

Permanently discontinue TAFINLAR for all grade 4 hemorrhagic events and for any grade 3 hemorrhagic events that do not improve. Withhold TAFINLAR for grade 3 hemorrhagic events; if improved, resume at the next lower dose level. Permanently discontinue MEKINIST for all grade 4 hemorrhagic events and for any grade 3 hemorrhagic events that do not improve. Withhold MEKINIST for grade 3 hemorrhagic events; if improved, resume at the next lower dose level.

Colitis and Gastrointestinal Perforation. Colitis and gastrointestinal perforation, including fatal outcomes, can occur. Across clinical trials of the combination, colitis occurred in <1% of patients and gastrointestinal perforation occurred in <1% of patients. Monitor patients closely for colitis and gastrointestinal perforations.

Venous Thromboembolic Events. Across clinical trials of the combination, deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 2% of patients. 

Advise patients to immediately seek medical care if they develop symptoms of DVT or PE, such as shortness of breath, chest pain, or arm or leg swelling. Permanently discontinue MEKINIST for life-threatening PE. Withhold MEKINIST for uncomplicated DVT and PE for up to 3 weeks; if improved, MEKINIST may be resumed at a lower dose level.

Cardiomyopathy. Cardiomyopathy, including cardiac failure, can occur. Across clinical trials of the combination, cardiomyopathy, defined as a decrease in left ventricular ejection fraction (LVEF) ≥10% from baseline and below the institutional lower limit of normal (LLN), occurred in 6% of patients. Development of cardiomyopathy resulted in dose interruption or discontinuation of TAFINLAR in 3% and <1% of patients, respectively, and in 3% and <1% of patients receiving MEKINIST, respectively. Cardiomyopathy resolved in 45 of 50 patients who received the combination.

Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of the combination, 1 month after initiation, and then at 2- to 3-month intervals while on treatment. Withhold TAFINLAR for symptomatic cardiomyopathy or asymptomatic left ventricular dysfunction of >20% from baseline that is below institutional LLN. Resume TAFINLAR at the same dose level upon recovery of cardiac function to at least the institutional LLN for LVEF and absolute decrease ≤10% compared to baseline. For an asymptomatic absolute decrease in LVEF of 10% or greater from baseline that is below the LLN, withhold MEKINIST for up to 4 weeks. If improved to normal LVEF value, resume at a lower dose. If no improvement to normal LVEF value within 4 weeks, permanently discontinue MEKINIST. For symptomatic cardiomyopathy or an absolute decrease in LVEF of >20% from baseline that is below LLN, permanently discontinue MEKINIST.

Ocular Toxicities.

Retinal Vein Occlusion (RVO): There were no cases of RVO across clinical trials of the combination. RVO may lead to macular edema, decreased visual function, neovascularization, and glaucoma.

Urgently (within 24 hours) perform ophthalmologic evaluation for patient-reported loss of vision or other visual disturbances. Permanently discontinue MEKINIST in patients with documented RVO.

Retinal Pigment Epithelial Detachment (RPED): RPED can occur. Retinal detachments may be bilateral and multifocal, occurring in the central macular region of the retina or elsewhere in the retina. In clinical trials, routine monitoring of patients to detect asymptomatic RPED was not conducted; therefore, the true incidence of this finding is unknown.

Perform ophthalmologic evaluation periodically, and at any time a patient reports visual disturbances. Withhold MEKINIST if RPED is diagnosed. If resolution of the RPED is documented on repeat ophthalmologic evaluation within 3 weeks, resume MEKINIST at the same or a reduced dose. If no improvement after 3 weeks, resume at a reduced dose or permanently discontinue MEKINIST.

Uveitis: Uveitis occurred in 2% of patients treated with the combination across trials. Treatment employed in clinical trials included steroid and mydriatic ophthalmic drops.

Monitor patients for visual signs and symptoms of uveitis (eg, change in vision, photophobia, and eye pain). If iritis is diagnosed, administer ocular therapy and continue TAFINLAR without dose modification. If severe uveitis (ie, iridocyclitis) or if mild or moderate uveitis does not respond to ocular therapy, withhold TAFINLAR and treat as clinically indicated. Resume TAFINLAR at the same or lower dose if uveitis improves to grade 0 or 1. Permanently discontinue TAFINLAR for persistent grade 2 or greater uveitis of >6 weeks.

Interstitial Lung Disease (ILD)/Pneumonitis. Across clinical trials of the combination, interstitial lung disease or pneumonitis occurred in 1% of patients.

Withhold MEKINIST in patients presenting with new or progressive pulmonary symptoms and findings including cough, dyspnea, hypoxia, pleural effusion, or infiltrates, pending clinical investigations. Permanently discontinue MEKINIST for patients diagnosed with treatment-related ILD or pneumonitis.

Serious Febrile Reactions. Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills, dehydration, or renal failure, can occur. The incidence and severity of pyrexia are increased when TAFINLAR is administered with MEKINIST.

Across clinical trials of the combination, fever occurred in 58% of patients. Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills, dehydration, or renal failure occurred in 5% of patients. Fever was complicated by hypotension in 4%, dehydration in 3%, syncope in 2%, renal failure in 1%, and severe chills/rigors in <1% of patients.

Withhold TAFINLAR and MEKINIST for temperature of ≥100.4ºF. In case of recurrence, therapy can also be interrupted at the first symptom of pyrexia. Fever may be complicated by hypotension, rigors or chills, dehydration, or renal failure. Evaluate for signs and symptoms of infection and monitor serum creatinine and other evidence of renal function during and following severe pyrexia. Upon 24 hours after resolution, if appropriate, resume both TAFINLAR and MEKINIST at the same or a lower dose. Administer antipyretics as secondary prophylaxis when resuming TAFINLAR and/or MEKINIST if the patient had a prior episode of severe febrile reaction or fever associated with complications. Administer corticosteroids (eg, prednisone 10 mg daily) for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of onset of pyrexia, or for pyrexia associated with complications such as hypotension, severe rigors or chills, dehydration, or renal failure, and there is no evidence of active infection.

Serious Skin Toxicities. Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with the combination. Across clinical trials of the combination, other serious skin toxicity occurred in <1% of patients. 

Monitor for new or worsening serious skin reactions. Permanently discontinue the combination for SCARs. For other skin toxicities, withhold TAFINLAR and/or MEKINIST for intolerable or severe skin toxicity. Resume TAFINLAR and/or MEKINIST at a lower dose in patients with improvement or recovery from skin toxicity within 3 weeks. Permanently discontinue TAFINLAR and/or MEKINIST if skin toxicity has not improved within 3 weeks.

Hyperglycemia. Across clinical trials of the combination, 15% of patients with a history of diabetes required more intensive hypoglycemic therapy. Grade 3 and grade 4 hyperglycemia occurred in 2% of patients.

Monitor serum glucose levels upon initiation and as clinically appropriate in patients with preexisting diabetes or hyperglycemia. Initiate or optimize antihyperglycemic medications as clinically indicated.

Glucose-6-Phosphate Dehydrogenase Deficiency. TAFINLAR, which contains a sulfonamide moiety, confers a potential risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Monitor patients with G6PD deficiency for signs of hemolytic anemia while taking TAFINLAR.

Embryo-fetal Toxicity. TAFINLAR and MEKINIST can cause fetal harm when administered to a pregnant woman. Advise female patients of reproductive potential to use effective nonhormonal contraception during treatment, and for 4 months after treatment.

Most Common Adverse Reactions. In the COMBI-d and COMBI-v studies, the most common adverse reactions (≥20%) for the combination were pyrexia (54%), nausea (35%), rash (32%), chills (31%), diarrhea (31%), headache (30%), vomiting (27%), hypertension (26%), arthralgia (25%), peripheral edema (21%), and cough (20%). In the COMBI-d and COMBI-v studies, the most common grade 3 or 4 adverse reactions (≥2%) for the combination were hypertension (11%), pyrexia (5%), and hemorrhage (2%). In the COMBI-AD study, the most common adverse reactions (≥20%) for the combination were pyrexia (63%), fatigue (59%), nausea (40%), headache (39%), rash (37%), chills (37%), diarrhea (33%), vomiting (28%), arthralgia (28%), and myalgia (20%). The most common grade 3 or 4 adverse reactions (≥2%) for the combination were pyrexia (5%) and fatigue (5%).

Other Clinically Important Adverse Reactions. In the COMBI-d and COMBI-v studies, other clinically important adverse reactions observed in <10% of patients receiving the combination were pancreatitis, panniculitis, bradycardia, and rhabdomyolysis. In the COMBI-AD study, other clinically important adverse reactions observed in <20% of patients receiving the combination were blurred vision (6%), decreased ejection fraction (5%), rhabdomyolysis (<1%), and sarcoidosis (<1%).

Laboratory Abnormalities. In the COMBI-d and COMBI-v studies, treatment-emergent laboratory abnormalities occurring in ≥10% of patients receiving the combination were hyperglycemia (60%), increased aspartate aminotransferase (AST) (59%), increased blood alkaline phosphatase (49%), increased alanine aminotransferase (ALT) (48%), hypoalbuminemia (48%), neutropenia (46%), anemia (43%), hypophosphatemia (38%), lymphopenia (32%), hyponatremia (25%), and thrombocytopenia (21%). In the COMBI-AD study, treatment-emergent laboratory abnormalities occurring in ≥20% of patients receiving the combination were hyperglycemia (63%), increased AST (57%), increased ALT (48%), neutropenia (47%), hypophosphatemia (42%), increased blood alkaline phosphatase (38%), lymphopenia (26%), anemia (25%), and hypoalbuminemia (25%).

Please see full Prescribing Information for TAFINLAR and full Prescribing Information for MEKINIST.