Clinical utility and patient considerations in the use of ofatumumab in chronic lymphocytic leukemia

Figures & data

Table 1 Clinical trials in previously untreated patients

Authors	Schedule	Patient number	ORR (%) (CRR %)	Follow-up (mo)	PFS (mo)	OS (mo)
Flinn et al 2012^Citation49	O: 300 mg D1; 2,000 mg D8; 2,000 mg weekly for 6 w; 2,000 mg monthly for 4 mo	42	44 (0)	NR	NR	NR
Ciccone et al 2014^Citation50	O: 300 mg D1; 2,000 mg D8; D15; D22 (C1); 2,000 mg monthly for 12 mo (O: 1,000 mg for the first 8 patients)	13	69 (23)	24	46%	92%
Jain et al 2013^Citation51	O: 300 mg D1, 1,000 mg weekly for 7 w	18	67 (17)	7.6	83%	100%
Ma et al 2014^Citation52	Alem 3 times/w up to 18 w O: (from w3): 300 mg D1; 2,000 mg q2 w doses week 2 to week 8 (early interruption based on response assessment)	31	97 (42)	NR	90%	94%
Wierda et al 2011^Citation53	F: 25 mg/m^2 D2–4 C: 250 mg/m^2 D2–4 + O: 300 mg D1C1 → 500 mg D1C2–6 vs O: 300 mg D1C1 → 1,000 mg D1C2–6 q28 × 6 cycles	31 vs 30	77 (32) vs 73 (50)	8	nr	nr
Shanafelt et al 2013^Citation54	P: 2 mg/m^2 C: 600 mg/m^2 O: C1 300 mg D1; 1,000 mg D8 C2–6 1,000 mg D1 q21 × 6 cycles	48	96 (46)	24 (living patients)	nr (TTR)	42 patients alive at 24 months
Montillo et al 2015^Citation55	P: 2mg/m^2 C: 600 mg/m^2 O: C1 300 mg D1; 1,000 mg D8 C2–6 1,000 mg D1 q21 × 6 cycles	47	89 (51)	22	nr	nr
Hillman et al 2015^Citation56	Chl: 10 mg/m^2 D1–7 q 28 up to 12 cycles vs O: C1 300 mg D1; 1,000 mg D8 C2–6 1,000 mg D1 + Chl: 10 mg/m^2 D1–7 q28 up to 12 cycles	226 vs 221	69 (1) vs 82 (14)	29	13 vs 22	nr nr
Offner et al 2014^Citation38	O: 300 mg C1D1, 1,000 mg C1D8; 1,000 mg D1C2 to C6 B: 90 mg/m^2 D1–2 C1 → 6	44	95 (48)	8.5	NR	NR

Abbreviations: O, ofatumumab; Alem, alemtuzumab; F, fludarabine; C, cyclophosphamide; P, pentostatin; Chl, chlorambucil; B, bendamustine; ORR, overall response rate; CR, complete response; CRR, complete remission rate; PFS, progression free survival; OS, overall survival; mo, month(s); NR, not reported; nr, not reached; D, day; w, week(s); TTR, time to retreatment; C, cycle.

Table 2 Clinical trials in relapsed/refractory patients

Authors	Schedule	Patient number	ORR (%) (CRR %)	Follow-up (mo)	PFS (mo)	OS (mo)
Coiffier et al 2008^Citation33	O: 100 mg → 500 mg	3	33	NR	2.6	NR
	O: 300 mg → 1,000 mg	3	0		2.5
	O: 500 mg → 2,000 mg	27	50		4.4
	For 4 infusions
Wierda et al 2010^Citation34	O: 300 mg D1; D8; 2,000 mg weekly for 6 w; 2,000 mg monthly for 4 mo FA-ref BF-ref	59 79	57 48	NR	5.7 5.9	13.7 15.4
Cortelezzi et al 2014^Citation37	O: 300 mg C1D1, 1,000 mg C1D8; 1,000 mg D1C2 → 6 B: 70 mg/m^2 D1–2 C1 to C6	47	72 (17)	24.2	49.6%	83.6%
Offner et al 2014^Citation38	O: 300 mg C1D1, 1,000 mg C1D8; 1,000 mg D1C2 → 6 B: 70 mg/m^2 D1–2 C1 → 6	53	74 (11)	8.7	nr	nr
Castro et al 2014^Citation40	O: 300 mg D1; 1,000 mg weekly for 12 w mPDN 1,000 mg/m^2 D1–3 q28	21	81 (5)	31	9.9	nr
Doubek et al 2015^Citation41	O: C1D1: 300 mg, D8, 15, 22: 2,000 mg; C2–6 D1, 8, 15, 22: 1,000 mg Dexa D1 → 4; 15 → 18 C1 → C6	33	67 (15)	NR	11	34
Costa et al 2015^Citation43	O: C1 → 6 2,000 mg D1 lenalidomide 10 mg D8 → 28 q28 for 6 C	21	47.6	16.1	nr	21.5
Byrd et al 2014^Citation64	O: 300 mg D1; 2,000 mg D8; 2,000 mg weekly for 6 w; 2,000 mg monthly for 4 mo vs ibrutinib 420 mg daily	196 vs 195	4 (0) vs 43 (0)	9.4	8.1 mo vs nr	nr in both (at 12 mo 81 vs 90%)
Jaglowski et al 2015^Citation65	O: 300 mg w5; 2,000 mg w6; 2,000 mg weekly for 6 w; 2,000 mg monthly for 4 mo + ibrutinib 420 mg daily from D1 O: starting from w1 D2 + ibrutinib 420 mg daily from w1 D1 O: starting from w1 D1 + ibrutinib 420 mg daily from w9	27 20 24	100 79 71	12.5	nr (at 12 mo 88.7%) nr (at 12 mo 85%) nr (at 12 mo 75%)	nr (at 12 mo 92.3%) nr (at 12 mo 85%) nr (at 12 mo 87.5)
Moreno et al 2015^Citation44	Observational	103	22 (3)	9.4	5	11
Chowdhury et al 2011^Citation45	Observational	27	48 (11)	8	5.5 (TTNT)	nr
Dupuis et al 2015^Citation46	Observational	30	47 (13)	8	4.3	8.3

Abbreviations: O, ofatumumab; B, bendamustine; Dexa, dexamethasone; mPDN, methylprednisolone; FA-ref, fludarabine refractory; BF-ref, bulky-fludarabine refractory; ORR, overall response rate; CR, complete response; CRR, complete remission rate; PFS, progression free survival; OS, overall survival; mo, month(s); NR, not reported; nr, not reached; D, day; w, week(s); C, cycle; TTNT, time to next treatment.

FlinnIWHarwinWNMacias-PérezIMA Phase II Trial of Ofatumumab for Older Patients and Patients Who Refuse Fludarabine-Based Regimens with Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaAbstract presented at: ASH Annual MeetingDecember 8–11, 2012Atlanta, GA

 Google Scholar

CicconeMVitaleCHinojosaCEarly Results of a Phase II Study of Ofatumumab As Front-Line Treatment in Elderly, Unfit Patients with Chronic Lymphocytic Leukemia (CLL)Abstract presented at: ASH Annual MeetingDecember 5–8, 2014San Francisco, CA

 Google Scholar

JainNKeatingMJFerrajoliAEarly Ofatumumab Treatment For High-Risk, Treatment-Naive Patients With Chronic Lymphocytic LeukemiaAbstract presented at: ASH Annual MeetingDecember 7–10, 2013New Orleans, LA

 Google Scholar

MaSRosenSFrankfurtOA Phase 2 Study of Alemtuzumab-Ofatumumab (A+O) Combination in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL)Abstract presented at: ASH Annual MeetingDecember 5–8, 2014San Francisco, CA

 Google Scholar

WierdaWGKippsTJDürigJChemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemiaBlood2011117246450645821498674

 PubMed Web of Science ®Google Scholar

ShanafeltTLanasaMCCallTGOfatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL)Cancer2013119213788379623922059

 PubMed Web of Science ®Google Scholar

MontilloMRossiDMottaMA Phase II Multi-Center Trial Of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) In Older Previously Untreated Chronic Lymphocytic Leukemia (CLL) PatientsAbstract presented at: ASH Annual MeetingDecember 7–10, 2013New Orleans, LA

 Google Scholar

HillmenPRobakTJanssensAChlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trialLancet2015385998018731883.25882396

 PubMed Web of Science ®Google Scholar

OffnerFPanagiotidisPAfanasyevBOfatumumab therapy in patients with untreated and relapsed chronic lymphocytic leukemia: initial results of the phase II study OMB115991Presented at: ASH MeetingDecember 5, 2014San Francisco, CA, USA

 Google Scholar

CoiffierBLepretreSPedersenLMSafety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1–2 studyBlood200811131094110018003886

 PubMed Web of Science ®Google Scholar

WierdaWGKippsTJMayerJOfatumumab as a single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemiaJ Clin Oncol201028101749175520194866

 PubMed Web of Science ®Google Scholar

CortelezziASciumèMLiberatiAMBendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II TrialLeukemia201428364264824220274

 PubMed Web of Science ®Google Scholar

CastroJEChoiMYCarvajalTOfatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemiaBlood Cancer J20144e25825397619

 PubMed Web of Science ®Google Scholar

DoubekMBrychtovaYPanovskaAOfatumumab added to dexamethasone in patients with relapsed or refractory chronic lymphocytic leukemia: Results from a phase II studyAm J Hematol201590541742125645263

 PubMed Web of Science ®Google Scholar

CostaLJFanningSRStephensonJJrSequential ofatumumab and lenalidomide for the treatment of relapsed and refractory chronic lymphocytic leukemia and small lymphocytic lymphomaLeuk Lymphoma201556364564925130476

 PubMed Web of Science ®Google Scholar

ByrdJCBrownJRO’BrienSIbrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid LeukemiaN Engl J Med2014371321322324881631

 PubMed Web of Science ®Google Scholar

JaglowskiSMJonesJANagarVSafety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 studyBlood Epub2015626

 Web of Science ®Google Scholar

MorenoCMontilloMPanayiotidisPOfatumumab in poor-prognosis chronic lymphocytic leukemia: a Phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic LeukemiaHaematologica2015100451151625596264

 PubMed Web of Science ®Google Scholar

ChowdhuryOVargheseAPattinsonJOfatumumab in advanced stage chronic lymphocytic leukaemia: results of the UK named patient compassionate use programmeBr J Haematol2011155451952121564074

 PubMed Web of Science ®Google Scholar

DupuisJBricePFrançoisSOfatumumab in refractory chronic lymphocytic leukemia: experience through the French early access programClin Lymphoma Myeloma Leuk20151524346

 Google Scholar