Table 3.

Fully published MAs and NMAs since 2016: safety outcomes [8,9,11,15,18,19,20,21,22,23].

Author, Year	NMA	Sponsored	N Studies (Patients)	Population	Intervention	Comparator	Outcome	Hazard Ratio or Risk Ratio (Confidence or Credible Intervals)
Wu, 2017 [19]	No	No	13 (2314)	R/R	Ofa-based	Non-Ofa-based	AE	Infections more frequent Thrombocytopenia & anemia less frequent
Pula, 2018 [18]	No	No	5 (1866)	R/R	BTK inhibitors	Non BTK inhibitors	AE HG AE disc AE death	1.25 (1.08–1.44) 1.26 (0.88–1.81) 1.06 (0.72–1.57)
Xu, 2018 [11]	Yes	Yes	15 (5300)	Naïve	I	Chl O-Chl R-Chl Ofa-Chl B	AE disc	0.32 (0.08–1.18) 0.31 (0.05–2.00) 0.66 (0.1–4.31) 0.31 (0.05–1.90) 0.08 (0.1–0.6)
				Naïve, FI	I	Chl O-Chl R-Chl Ofa-Chl B	AE disc	0.23(0.15–0.63) 0.31(0.11–0.80) 0.65 (0.23–1.81) 0.31(0.12–0.77) 0.08(0.02–0.7)
Zhou 2019 [21]	No	No	5 (2456)	Naïve, R/R	I	Mixed	Anemia Thrombocytopenia Neutropenia Febrile neutropenia Respiratory tract infections Abdominal AE Arthralgia	0.90 (0.67–1.21) 0.61 (0.32–1.14) 0.50 (0.25–1.00) 0.89 (0.32–2.49) 1.01 (0.78–1.30) 2.14 (1.44–3.17) 1.86 (1.10–3.15)
Caldeira, 2019 [23]	No	No	8 (2580)	CLL &	I-based therapy	Mixed	Arterial hypertension Atrial fibrillation	2.82 (1.52–5.23) 4.69 (2.17–7.64)
Wang 2020 [22]			11 (4288)	CLL &	I	Mixed	Bleeding Major bleed	3.08 (2.07–4.58) 2.46 (1.37–4.41)
Ball, 2020 [20]	No	No	5 (1739)	Naïve, R/R	I	Mixed	Infections HG	1.24 (1.02–1.50)
Lee, 2020 [15]	No	Yes	6 (1615)	R/R	Lenalidomide (maint) R (maint) Ofa (maint)	No maintenance	AE	1.84 (0.98–3.43) 1.11 (0.69–1.79) 2.11 (0.92–4.81)
Sheng, 2020 [9]	Yes	No	3 (1017)	Naïve	OA	OI	AE disc Grade 3–4 AE Any AE	0.64 (0.11–1.86) 1.10 (0.52–2.32) 0.48 (0.01–48.20)
					OA	OV	AE disc Grade 3–4 AE Any AE	0.68 (0.26–1.81) 5.28 (0.03–831.44) 0.89 (0.45–1.77)
Molica, 2020 CLM [8]	Yes	No	3 (1027)	Naïve	VO A A	IO IO VO	Grade 3–4 AE	1.05 (0.64–1.73) 0.73 (0.43–1.24) 0.69 (0.44–1.09)

Bolded risk ratios show significantly increased (or reduced) hazards of adverse events of intervention versus comparator. Legend: A—acalabrutinib; AE—adverse effects; AE disc—discontinuation for an AE; BR—bendamustine plus rituximab; Chl—chlorambucil; F—fludarabine; FC—fludarabine and cyclo; A—acalabrutinib; BR—bendamustine plus rituximab; Chl—chlorambucil; F—fludarabine; FC—fludarabine and cyclophosphamide; FCR—fludarabine plus cyclophosphamide plus rituximab; FI—fludarabine ineligible; HG—grade 3–5; HR—hazard ratio; I—ibrutinib; IGV—immunoglobulin heavy chain variable region; IR—ibrutinib plus rituximab; maint—maintenance; mut—mutated status; O—obinutuzumab; O-Chl—obinutuzumab plus chlorambucil; OA—obinutuzumab plus acalabrutinib; Ofa—ofatumumab; Ofa-Chl—ofatumumab plus chlorambucil; OI—obinutuzumab plus ibrutinib; OS—overall survival; OV—obinutuzumab plus venetoclax; PFS—progression-free survival; R—rituximab; R-Chl—chlorambucil plus rituximab; R/R—relapsed/refractory; RB—rituximab plus bendamustine; RV—rituximab plus venetoclax; V—venetoclax; unmut—unmutated status.