Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Regimen Options

Last Updated: 12/20/2024 See Details

NOTE: FOR RITUXIMAB, THE USE OF A BIOSIMILAR OR THE REFERENCE PRODUCT IS ON PATHWAY

	Evolent Pathways	Febrile Neutropenic Risk	Emetogenic Risk	References
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) / SMALL LYMPHOCYTIC LYMPHOMA (SLL)
Initial therapy: WITHOUT del (17p)/ TP53 mutation	acalabrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Byrd JC et al. N Engl J Med . 2016 Jan 28;374(4):323-32.. Sharman JP et al. https://doi.org/10.1182/blood-2019-128404
	ibrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Byrd JC et al. DOI: 10.1200/JCO.21.01210 Journal of Clinical Oncology
	zanubrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.2.2023. Tam CS et al. Lancet Oncol . 2022 Aug;23(8):1031-1043.
	bendamustine and rituximab	Intermediate	Moderate	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Fischer K, et al. J Clin Oncol. 2012;30(26):3209-16. Fischer K, et al. J Clin Oncol. 2011;29(26):3559-66. Eichhorst B, et al. Lancet Oncol. 2016;17(7):928-42.
	FCR (Fludarabine, cyclophosphamide, and rituximab) for patients w/mutated IgHV	Intermediate	Moderate	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Hallek M, et al. Lancet. 2010;376(9747):1164-74. Fischer K, et al. Blood. 2016;127(2):208-15.
	venetoclax + obinutuzumab (fixed duration of ~12 months)	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Al-Sawaf O et al. Lancet Oncol 2020; 21: 1188–200
Initial therapy: WITH del (17p)/ TP53 mutation	acalabrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Byrd JC et al. N Engl J Med . 2016 Jan 28;374(4):323-32.. Sharman JP et al. https://doi.org/10.1182/blood-2019-128404
	ibrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Byrd JC et al. DOI: 10.1200/JCO.21.01210 Journal of Clinical Oncology
	zanubrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.2.2023. Tam CS et al. Lancet Oncol . 2022 Aug;23(8):1031-1043.
	venetoclax + obinutuzumab (fixed duration of ~12 months)	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Al-Sawaf O et al. Lancet Oncol 2020; 21: 1188–200
Subsequent Therapy: WITH del (17p)/ TP53 mutation	acalabrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Byrd JC et al. N Engl J Med . 2016 Jan 28;374(4):323-32.. Sharman JP et al. https://doi.org/10.1182/blood-2019-128404
	zanubrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.2.2023. Tam CS et al. Lancet Oncol . 2022 Aug;23(8):1031-1043.
	venetoclax	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Stilgenbauer S, et al. Blood. 2015;126:Abstract LBA-6. Roberts AW, et al. N Engl J Med. 2016;374:311-322 Seymour JF, Kipps TJ, Eichhorst B, N Engl J Med. 2018 Mar 22;378(12):1107-1120.
	venetoclax and rituximab	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Stilgenbauer S, et al. Blood. 2015;126:Abstract LBA-6. Roberts AW, et al. N Engl J Med. 2016;374:311-322 Seymour JF, Kipps TJ, Eichhorst B, N Engl J Med. 2018 Mar 22;378(12):1107-1120.
Subsequent Therapy: WITHOUT del (17p)/ TP53 mutation	acalabrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Byrd JC et al. N Engl J Med . 2016 Jan 28;374(4):323-32.. Sharman JP et al. https://doi.org/10.1182/blood-2019-128404. Byrd JC et al. DOI: 10.1200/JCO.21.01210 Journal of Clinical Oncology
	zanubrutinib	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Brown, JR et al. N Engl J Med 2023; 388:319-332
	bendamustine and rituximab	Intermediate	Moderate	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Fischer K, et al. J Clin Oncol. 2012;30(26):3209-16. Fischer K, et al. J Clin Oncol. 2011;29(26):3559-66. Eichhorst B, et al. Lancet Oncol. 2016;17(7):928-42.
	venetoclax	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Stilgenbauer S, et al. Blood. 2015;126:Abstract LBA-6. Roberts AW, et al. N Engl J Med. 2016;374:311-322 Seymour JF, Kipps TJ, Eichhorst B, N Engl J Med. 2018 Mar 22;378(12):1107-1120.
	venetoclax and rituximab	Low	Low	NCCN Guidelines® for Chronic Myeloid Leukemia/ Small Lymphocytic Lymphoma. V.1.2018. Stilgenbauer S, et al. Blood. 2015;126:Abstract LBA-6. Roberts AW, et al. N Engl J Med. 2016;374:311-322 Seymour JF, Kipps TJ, Eichhorst B, N Engl J Med. 2018 Mar 22;378(12):1107-1120.
	Best Supportive Care or Clinical Trial	Not Applicable	Not applicable	NCCN Guidelines® for Supportive Care

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) / SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Initial therapy: WITHOUT del (17p)/ TP53 mutation

Evolent Pathways

acalabrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

ibrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

zanubrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

bendamustine and rituximab

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

FCR (Fludarabine, cyclophosphamide, and rituximab) *for patients w/mutated IgHV*

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

venetoclax + obinutuzumab (fixed duration of ~12 months)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Initial therapy: WITH del (17p)/ TP53 mutation

Evolent Pathways

acalabrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

ibrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

zanubrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

venetoclax + obinutuzumab (fixed duration of ~12 months)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Subsequent Therapy: WITH del (17p)/ TP53 mutation

Evolent Pathways

acalabrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

zanubrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

venetoclax

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

venetoclax and rituximab

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Subsequent Therapy: WITHOUT del (17p)/ TP53 mutation

Evolent Pathways

acalabrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

zanubrutinib

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

bendamustine and rituximab

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

venetoclax

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

venetoclax and rituximab

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

Best Supportive Care or Clinical Trial

Febrile Neutropenic Risk

Emetogenic Risk

References

	Regimen	Alternative
LOW VALUE REGIMENS (NON-PATHWAY) WITH SUPERIOR ALTERNATIVES
Initial therapy	acalabrutinib and obinutuzumab with or without del(17p)/TP53 mutation	Alternative: acalabrutinib
Initial therapy	ibrutinib and obinutuzumab without del(17p)/TP53 mutation	Alternative: acalabrutinib
Initial therapy	ibrutinib and rituximab without del(17p)/TP53 mutation	Alternative: acalabrutinib
Subsequent Therapy	lenalidomide with or without rituximab with or without del (17p)/ TP53 mutation	Alternative: bendamustine + rituximab

LOW VALUE REGIMENS (NON-PATHWAY) WITH SUPERIOR ALTERNATIVES

Initial therapy

Regimen

acalabrutinib and obinutuzumab *with or without del(17p)/TP53 mutation*

Initial therapy

Regimen

ibrutinib and obinutuzumab *without del(17p)/TP53 mutation*

Initial therapy

Regimen

ibrutinib and rituximab *without del(17p)/TP53 mutation*

Subsequent Therapy

Regimen

lenalidomide with or without rituximab *with or without del (17p)/ TP53 mutation*

Pathways and Low-Value Regimens

Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)