TREATMENT CONSIDERATIONS IN CLL/SLL AND FL. June 6, 2018

Transcription

1 TREATMENT CONSIDERATIONS IN CLL/SLL AND FL June 6,

2 PRESENTATION OVERVIEW IN CLL/SLL AND FL: Discuss key considerations that influence patient outcomes Highlight the importance of patients quality of life Review treatment considerations 1

3 2 KEY CONSIDERATIONS IN CLL/SLL AND FL

4 MOST PATIENTS WITH CLL/SLL AND FL ARE ELDERLY Key Considerations CLL/SLL FL CLL/SLL tends to impact the elderly population, with a median age of diagnosis of 72 years 1 FL also tends to impact the elderly population, with a median age of diagnosis of 65 years 2 3 CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; FL, follicular lymphoma; NHL, non-hodgkin lymphoma. 1. Gribben JG. Expert Rev Anticancer Ther. 2010;10(9): Castellino A, Santambrogio E, Nicolosi M, et al. Follicular lymphoma: the management of elderly patient. Mediterr J Hematol Infect Dis. 2017; 9(1): National Cancer Institute Non-Hodgkin Lymphoma-Cancer Stat Facts. Accessed April 3, 2018.

5 KEY CONSIDERATIONS FOR TREATMENT IN CLL/SLL AND FL Key Considerations It is important to identify factors that may interfere with treatment because of the aging population and increased life expectancy in patients with CLL/SLL and FL 1,2 The potential for drug drug interactions due to polypharmacy, poor access to nutrition, inadequate social support, depression, and other coexisting illnesses may affect the therapeutic effect of the proposed treatment plan 1 The patient s therapy needs to be individualized based on the specific clinical presentation and maintaining quality of life 1, Barrientos JC. Cancer Control. 2015;22(40): Castellino A et al. Mediterr J Hematol Infect Dis. 2017;9(1):e Molica S. Leuk Lymphoma. 2005;46(12):

6 PATIENTS OFTEN HAVE COMORBIDITIES THAT MAY IMPACT TREATMENT OPTIONS, PROGNOSIS, AND RESPONSE Key Considerations CLL/SLL Individualized patient care is increasingly important for patients with multiple cormorbidities 1 The most common comorbidities in CLL patients include hypertension, rheumatological conditions, and hyperlipidemia 2 FL While comorbidities are not related to the disease state, they can be negatively associated with patient outcomes, such as overall survival 4 The most common comorbidities in FL patients include cardiovascular, vascular, and respiratory disorders 4 CIRS, Cumulative Illness Rating Scale Goede V et al. Haematologica. 2014;99: Thurmes P et al. Leuk Lymphoma. 2008;49(1): Gribben JG. Expert Rev Anticancer Ther. 2010;10: Nabhan M et al. Br J Haematol. 2012;156(2):

7 COMORBIDITIES IN ELDERLY PATIENTS INCREASE SAFETY RISKS Key Considerations Treatment-related complications may arise or worsen in patients harboring specific comorbidities 5 Patient comorbidities should therefore be considered when choosing an appropriate treatment 5 6 Bcl-2, B-cell lymphoma 2; BTK, Bruton s tyrosine kinase; CV, cardiovascular; PI3K, phosphoinositide 3-kinase. 1. Hurria A et al. J Clin Oncol. 2011;29(25): Lipsky AH et al. Haematol. 2015;100(12): Brown JR et al. Haematol. 2017;102(10): Coutre SE et al. Leuk Lymphoma. 2015;56(10): Goede V et al. Haematologica. 2014;99:

8 PROGNOSTIC FACTORS IN ELDERLY PATIENTS WITH CLL/SLL AND FL Key Considerations Certain prognostic factors significantly correlate with negative outcomes (PFS and OS) 1,2 Poor ECOG performance status, poor mental health, and polypharmacy can also impact treatment outcomes in elderly patients 1 In patients with indolent NHLs, poor ECOG performance status and the presence of B symptoms were among factors most predictive for inferior survival 2 Adapted from Nabhan et al ECOG PS, Eastern Cooperative Oncology Group Performance Status; LDH, lactate dehydrogenase; PFS, progression-free survival; OS, overall survival; ULN, upper limit of normal. 1. Barrientos JC. Cancer Control. 2015;22(40): Nabhan C et al. Br J Haematol. 2012;156(2):

9 8 QUALITY-OF-LIFE CONSIDERATIONS

10 RELEVANCE OF QUALITY OF LIFE (QOL) FOR CLL/SLL AND FL Quality of Life CLL/SLL and FL are indolent in nature and QoL may be an important consideration when selecting treatment 1,2 QoL is a particularly important consideration when selecting long-term treatment options 2 CLL/SLL and FL are incurable cancers where long-term treatment may extend disease-free survival 3 Thus, new treatment options that offer patient convenience with manageable safety profiles should be considered Beaven AW et al. Cancer Invest. 2016;34(6): Shanafelt TD et al. Br J Haematol. 2007;139: Molica S. Leuk Lymphoma. 2005;46(12): Lamanna N et al. Hematology Am Soc Hematol Educ Program. 2016;(1): Meropol NJ et al. Cancer. 2008;113(12):

11 IMPACT OF QOL ALONG THE CLL/SLL PATIENT JOURNEY Quality of Life Disease-related symptoms, toxic effects of therapy, and the awareness of living with an incurable disease can have a profound impact on health-related quality of life (HRQoL) 1 Once treatment is initiated, HRQoL becomes considerably compromised 1 HRQoL, Health-related quality of life Holtzer-Goor KM et al. Qual Life Res. 2015;24: National Comprehensive Cancer Network, Inc. CLL/SLL Guidelines, Version National Comprehensive Cancer Network, Inc. B-Cell Lymphomas Guidelines Version

12 EMOTIONAL WELL-BEING IS LOWER IN CLL PATIENTS THAN IN OTHER CANCER PATIENTS Quality of Life CLL Patients with CLL may suffer greater emotional distress due to the watch-and-wait approach of early stage disease because they assume that nothing is being done QoL for CLL patients, other cancer patients, and healthy patients. Patients with CLL had a significantly lower emotional well-being than both other populations. CLL, n=846; Other, n=964; Healthy, n=516. FACT-G, Functional Assessment of Cancer Therapy General scale. 11 Shanafelt TD et al. Br J Haematol. 2007;139(2):

13 CHEMOIMMUNOTHERAPY MAY LEAD TO DEPRESSION IN PATIENTS WITH FL Quality of Life FL Patients with FL who received chemoimmunotherapy experienced significantly worse depression than those off chemoimmunotherapy *HADS-D scores of patients with FL on and off chemoimmunotherapy. n= Pettengell R et al. Ann Oncol. 2008;19:

14 13 TREATMENT CONSIDERATIONS IN CLL/SLL AND FL

15 ADMINISTRATION IS AN IMPORTANT COMPONENT OF THE OVERALL TREATMENT EXPERIENCE IN ONCOLOGY Treatment Considerations One component of the patient treatment experience is how therapy is administered 1 Patient preference plays a role in treatment selection (oral vs IV) 2 Orally administered cancer drugs offer patients greater flexibility than IV treatment 1 Studies have shown that patients with incurable malignancies prefer oral to IV drugs due to a perception of greater level of QoL Eek D et al. Patient Prefer Adherence. 2016;10: Biganzoli L et al. Eur J Cancer. 2015;51:

16 IV-BASED TREATMENTS CAN NEGATIVELY IMPACT THE PATIENT EXPERIENCE Treatment Considerations IV-based treatments can impose a significant safety burden on patients 1,2 IV-based therapies can lead to IVrelated infections, erythema, and venous thrombosis 1 Ultimately, patients may benefit from a needle-free option to avoid IV-related AEs 2 AE, adverse events; IV, intravenous infusion Mattox E. Crit Care Nurse. 2017;37(2):e1-e Schott S et al. BMC Cancer. 2011;11(129):1-10.

17 ORAL MONOTHERAPIES ARE A CONVENIENT ALTERNATIVE TO IV THERAPIES Treatment Considerations Schott S et al. BMC Cancer. 2011;11(129): Eek D et al. Patient Prefer Adherence. 2016;10: Chekerov R et al. Gynecol Oncol Res Pract. 2017;4(6): Bordonaro S et al. World Cancer Res J. 2014;1(2):e223.

18 WHEN SELECTING TARGETED THERAPIES, SIDE EFFECT PROFILE IS AN IMPORTANT CONSIDERATION Treatment Considerations The selective nature of novel targeted agents in CLL/SLL and FL exhibit well-characterized and ontarget safety profiles 1,2 Side effect profiles may play an important role in treatment selection for CLL/SLL and FL patients 1 A careful risk assessment should be made for elderly patients who may have reduced treatment tolerance Lamanna N et al. Hematology Am Soc Hematol Educ Program. 2016;2016(1): Sehn LH. Hematology Am Soc Hematol Educ Program. 2016;2016(1): Stauder R et al. Ann Oncol. 2017;28: Aliqopa Prescribing Information. 5. Barrientos JC. Cancer Control. 2015;22(40):17-23.

19 TARGETED AGENTS HAVE INCREASED THE RISK OF TUMOR LYSIS SYNDROME Treatment Considerations Tumor lysis syndrome (TLS) is a potentially life-threatening condition caused by the abrupt release of cellular components into the bloodstream after massive lysis of malignant cells This complication can occur after the initiation of chemotherapy, Bcl-2 inhibitors, or other targeted therapies The introduction of targeted agents like Bcl-2 inhibitors in CLL/SLL that can cause rapid tumor reduction has increased the risk for TLS in these patients Cases of TLS have been reported in CLL/SLL patients taking Bcl-2 inhibitors, BTK inhibitors, and anti-cd20 monoclonal antibodies 18 Cheson BD et al. Oncologist. 2017;22(11):

20 TARGETED ORAL THERAPIES CAN ADDRESS SEVERAL TREATMENT CONSIDERATIONS WITHOUT COMPROMISING EFFICACY Treatment Considerations Rai KR. Hematol Oncol. 2015;8: Vitale C et al. Expert Opin Pharmacother. 2017;18(4):

21 KEY TAKEAWAYS The majority of patients with CLL/SLL and FL are elderly with comorbid conditions, so particular attention must be paid to treatment administration route, safety profiles, and overall quality of life The importance of quality of life is elevated in CLL/SLL and FL because of their indolent nature and the potential for long-term treatment An oral dosing regimen is a convenient alternative to IV due to its at-home administration, predictable routine, and preference by patients Targeted therapies may be an appropriate option for a range of patient populations with diverse characteristics Treatment with on-target safety profiles may be important for elderly patients or those with other comorbidities 20