Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2 immunotherapy and isotretinoin: a prospective Phase II study

Figures & data

Table 1. Salvage therapy for relapse before enrollment of 101 study patients

Radiotherapy (local)	91 (90%)
Irinotecan^24,32,33	81 (80%)
Topotecan^24,31,34,35	69 (68%)
Temozolomide^32,33	68 (67%)
High-dose cyclophosphamide	65 (64%)
Surgical resection of disease	49 (49%)
High-dose cisplatin or carboplatin	31 (31%)
Investigative therapy	40 (40%)
^131I-MIBG	6 (6%)
Autologous stem cell transplantation	5 (5%)

^a 140 mg/kg or 4200 mg/m² per course^.6,24

^b cisplatin 200 mg/m² per course; carboplatin ≥1000 mg/m² per course^.6,33,36

Figure 1. Progression-free survival and overall survival of all 101 patients enrolled on the 03–077 protocol for consolidation of second or later complete/very good partial remission.

Table 2. Univariate analyses of patient and tumor characteristics for survival

Variable	Description	N	PFS		OS
			No. of events	P-value	No. of events	P-value
All Patients		101	64	−	54
Age at diagnosis, median (range)	3.3 (0.03 – 13.1)	101	64	0.285	54	0.230
MYCN amplification	yes	44	24	0.34	20	0.29
	no	53	36		32
	unknown	4	4		2
LDH at diagnosis	>1500	26	16	0.88	14	0.45
	≤1500	43	29		21
	unknown	32	19		19
Bony metastasis	yes	78	50	0.97	41	0.53
	no	23	14		13
Bone marrow metastasis	yes	79	50	0.91	44	0.47
	no	22	14		10
Time to first relapse	<12 m	14	8	0.97	7	0.97
	12–24 m	55	35		31
	>24 m	32	21		16
Isolated CNS relapse	yes	20	6	0.001	7	0.02
	no	81	58		47
Prior history of 3F8 or ch14.18	no	51	33	0.50	30	0.18
	yes	50	31		24
Remission# + h/o 3F8	2nd no h/o 3F8	42	28	0.78	25	0.61
	2nd h/o 3F8	46	29		22
	≥3rd no h/o 3F8	9	6		5
	≥3rd h/o 3F8	4	3		2
Remission #	2nd	88	55	0.41	47	0.76
	3rd	13	9		7
Pre-MRD	no	67	41	0.41	32	0.06
	yes	34	23		22
Post-MRD	no	70	39	<0.001	31	<0.001
	yes	25	22		20
	unknown	6	3		3
HAMA	yes	76	42	0.180	35	0.006
	no	25	22		19
Rituximab	yes	30	15	0.92	9	0.06
	no	46	27		26
Maintenance chemotherapy	yes	25	7	0.007	9	0.059
	no	51	35		26

Note. h/o, history of; LDH, lactate dehydrogenase.

* Rituximub and maintenance (temozolomide) chemotherapy were tested as time-dependent variables in the cohort of HAMA-positive patients only, where PFS and OS were calculated from time of HAMA.

** Rituximab cleared HAMA in 16 of these patients within 90 d.

*** Event-free survivors received 1–5 cycles of either temozolomide monotherapy⁴⁸ or irinotecan/temozolomide.³²

Figure 2. Strong association between minimal residual disease status after 2 cycles of 3F8 therapy (post-MRD) and progression-free survival probability (P < 0.001).

Figure 3. Strong association between minimal residual disease status after 2 cycles of 3F8 therapy (post-MRD) and overall survival probability (P < 0.001).

Table 3: Multivariate analysis of prognostic factors for survival

	PFS				OS
Prognostic Variable	HR	HR	HR	P	HR	HR 95% lower boundary	HR 95% upper boundary	P
Early post-treatment MRD	2.729	1.595	4.669	< 0.001	3.513	1.98	6.23	< 0.001
Isolated CNS relapse (Y vs. N)	0.307	0.131	0.718	0.006	0.558	0.246	1.266	0.163
HAMA					0.485	0.267	0.882	0.018

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Eng J Med 2005; 352:987-96; PMID:15758009; http://dx.doi.org/10.1056/NEJMoa043330

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