Table 3b. . Unexpectedly, SC rituximab did not induce diminution of natural killer cell levels in sharp difference to intravenous rituximab, even when infusions of lymphokine-activated killer cells (enriched with ‘classical warriors’ such as CD56+ natural killer and γδ T cells’ in these patients.
| Protocol | U-Mann p < 0.05 | N | U-Mann p < 0.05 | NS p > 0.05 | Age | Gender | Ann Arbor stage | IV R-CHOP+ LAKs | Status | Second line |
|---|---|---|---|---|---|---|---|---|---|---|
| LFNK | NK (after R-CHOP) | NK (1 Ritux IV) | NK (3 Ritux IV) | NK (6 Ritux IV) | ||||||
| 73 | 176 | 217 | 215 | 52 | Female | IV-B | 6 | CR | ||
| 27 | 188 | 176 | 132 | 49 | Female | IV-B | 6 | CR | Regional radiotherapy | |
| 65 | 103 | 85 | 230 | 64 | Male | IV-B | 6 | CR | ||
| 66 | 95 | 132 | 195 | 64 | Female | IV-B (spleen) | 6 | CR | ||
| 73 | 52 | 74 | 117 | 80 | Female | III-A | 6 | CR | ||
| Xme | 66 | 103 | 132 | 195 | ||||||
| (Xmin–Xmax) | (27–73) | (52–188) | (74–217) | (117–230) | ||||||
| NS | Sign test p = 0.025 | Sign test p = 0.025 | ||||||||
| MABRELLA | NK(after R-CHOP) | NK (1 sc Ritux) | NK (3 sc Ritux) | NK (6 sc Ritux) | Age | Gender | Ann Arbor stage | R-CHOP+ sc R main | Status | Second line |
| 95 | ND | 329 | 230 | 78 | Female | III-A | 8 | CR | ||
| 124 | 180 | 184 | 117 | 83 | Female | IV-B | 6 | CR | ||
| 230 | 232 | 333 | 498 | 68 | Male | IV-A | 6 | R/R | R-ESHAP + ASCT | |
| 177 | 162 | 233 | 228 | 67 | Female | IV-B | 8 | CR | ||
| 291 | 341 | 423 | 369 | 79 | Female | IV-A | 6 | CR | ||
| Xme | 177 | 206 | 329 | 230 | ||||||
| (Xmin–Xmax) | (95–291) | (162–341) | (184–423) | (117–498) | ||||||
| ND | Sign test p = 0.025 | Sign test p = 0.179 |
Bold details are to differentiate patients with subcutaneous (MABRELLA) or intravenous rituximab (LFNK).
This may represent a model in which immediate encounter of NK cells with anti-CD20 monoclonal antibodies in blood may prepare them to fight and migrate to secondary lymphoid organs ‘searching the enemy’. In contrast, SC rituximab unmasks enemies in secondary lymphoid organs to be recognized by ‘classical warriors’ such as NK and γδ T cells when they perform their normal immunosurveillance and discover tumoral cells coated with monoclonal antibodies.
ASCT: Autologous peripheral blood stem cell transplant; CHOP: Cyclophosphamide–doxorubicin–vincristine–prednisone; ESHAP: Etoposide-solumedrol-ARA-C-cisplatin; LAK: Lymphokine-activated killer; ND: Not done; NK: Natural killer; NS: Not significant; R: Rituximab; R-ESHAP: Rituximab-Etoposide-solumedrol-ARA-C-Cisplatin; CR: Complete response; R/R: Relapsed or refractory; SC: Subcutaneous; Xmax: Maximal value; Xme: Median X value; Xmin: Minimum X value.