TY - JOUR
T1 - Risk-adapted, ofatumumab-based chemoimmunotherapy and consolidation in treatment-naïve chronic lymphocytic leukemia
T2 - a phase 2 study
AU - Desai, Sanjal
AU - Mo, Clifton
AU - Gaglione, Erika M.
AU - Yuan, Constance M.
AU - Stetler-Stevenson, Maryalice
AU - Tian, Xin
AU - Maric, Irina
AU - Wake, Laura
AU - Farooqui, Mohammed Z.
AU - Drinkwater, Dennis C.
AU - Soto, Susan
AU - Valdez, Janet
AU - Hughes, Thomas E.
AU - Nierman, Pia
AU - Lotter, Jennifer
AU - Marti, Gerald E.
AU - Pleyer, Christopher
AU - Sun, Clare
AU - Superata, Jeanine
AU - Nichols, Cydney
AU - Herman, Sarah E.M.
AU - Lindorfer, Margaret A.
AU - Taylor, Ronald P.
AU - Wiestner, Adrian
AU - Ahn, Inhye E.
N1 - Publisher Copyright:
©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law.
PY - 2021
Y1 - 2021
N2 - High-risk cytogenetics and minimal residual disease (MRD) after chemoimmunotherapy (CIT) predict unfavorable outcome in chronic lymphocytic leukemia (CLL). This phase 2 study investigated risk-adapted CIT in treatment-naïve CLL (NCT01145209). Patients with high-risk cytogenetics received induction with fludarabine, cyclophosphamide, and ofatumumab. Those without high-risk cytogenetics received fludarabine and ofatumumab. After induction, MRD positive (MRD+) patients received 4 doses of ofatumumab consolidation. MRD negative (MRD-) patients had no intervention. Of 28 evaluable for response, all responded to induction and 10 (36%) achieved MRD-. Two-year progression-free survival (PFS) was 71.4% (CI95, 56.5–90.3%). There was no significant difference in median PFS between the high-risk and the standard-risk groups. Ofatumumab consolidation didn’t convert MRD + to MRD-. In the MRD + group, we saw selective loss of CD20 antigens during therapy. In conclusion, risk-adapted CIT is feasible in treatment-naïve CLL. Ofatumumab consolidation didn’t improve depth of response in MRD + patients. Loss of targetable CD20 likely reduces efficacy of consolidation therapy.
AB - High-risk cytogenetics and minimal residual disease (MRD) after chemoimmunotherapy (CIT) predict unfavorable outcome in chronic lymphocytic leukemia (CLL). This phase 2 study investigated risk-adapted CIT in treatment-naïve CLL (NCT01145209). Patients with high-risk cytogenetics received induction with fludarabine, cyclophosphamide, and ofatumumab. Those without high-risk cytogenetics received fludarabine and ofatumumab. After induction, MRD positive (MRD+) patients received 4 doses of ofatumumab consolidation. MRD negative (MRD-) patients had no intervention. Of 28 evaluable for response, all responded to induction and 10 (36%) achieved MRD-. Two-year progression-free survival (PFS) was 71.4% (CI95, 56.5–90.3%). There was no significant difference in median PFS between the high-risk and the standard-risk groups. Ofatumumab consolidation didn’t convert MRD + to MRD-. In the MRD + group, we saw selective loss of CD20 antigens during therapy. In conclusion, risk-adapted CIT is feasible in treatment-naïve CLL. Ofatumumab consolidation didn’t improve depth of response in MRD + patients. Loss of targetable CD20 likely reduces efficacy of consolidation therapy.
KW - Chronic lymphocytic leukemia
KW - chemoimmunotherapy
KW - minimal residual disease
KW - ofatumumab
KW - trogocytosis
UR - http://www.scopus.com/inward/record.url?scp=85111993417&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111993417&partnerID=8YFLogxK
U2 - 10.1080/10428194.2021.1888379
DO - 10.1080/10428194.2021.1888379
M3 - Article
C2 - 33653216
AN - SCOPUS:85111993417
SN - 1042-8194
VL - 62
SP - 1816
EP - 1827
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -
