Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy

Abstract

Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are prone to present with antibody production deficits associated with recurrent or severe bacterial infections that might benefit from human immunoglobulin (Ig) (IVIg/SCIg) replacement therapy. However, the original IVIg trial data were done before modern therapies were available, and the current indications do not take into account the shift in the immune situation of current treatment combinations and changes in the spectrum of infections. Besides, patients affected by other B cell malignancies present with similar immunodeficiency and manifestations while they are not covered by the current IVIg indications. A potential beneficial strategy could be to vaccinate patients at monoclonal B lymphocytosis and monoclonal gammopathy of undetermined significance stages (for CLL and MM, respectively) or at B-cell malignancy diagnosis, when better antibody responses are attained. We have to re-emphasize the need for assessing and monitoring specific antibody responses; these are warranted to select adequately those patients for whom early intervention with prophylactic anti-infective therapy and/or IVIg is preferred. This review provides an overview of the current scenario, with a focus on prevention of infection in patients with hematological malignancies and the role of Ig replacement therapy.

Current clinical practice and challenges in the management of secondary immunodeficiency in hematological malignancies

“…23 This divergence between recommendations and clinical practice points to the need for clinical studies to evaluate the use of IgRT at an early stage in a patient's primary disease, as suggested previously. 11,34 The high reported use of prophylactic antibiotics in the UK is consistent with reports of 85% of British and Irish immunologists prescribing prophylactic antibiotics in all, or most, of their patients before starting Ig therapy. 24 These observations might be explained by the inclusion of recurrent or severe bacterial infections despite continuous oral antibiotic therapy for 3 months as selection criteria for IgRT in the British clinical guidelines for Ig use.…”

“…In addition, in Canada, France, Germany, and the UK, the reported sessing and monitoring specific antibody responses. 11,34 In this online survey, over one-third of respondents did not measure specific antibody responses, while immunologists were much more likely to measure specific antibody responses. Contrary to recommendations to systematically perform test immunizations in patients with SID, only one-third (33%) of surveyed physicians did so on average.…”

Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression

“… 15 Thus, response to vaccination against both polysaccharide (e.g. classical multivalent pneumococcal vaccines 32 , 33 ) and protein antigens (e.g. tetanus toxoid and influenza virus 34 , 35 ) has been shown to be associated with poor seroprotective responses in CLL, even after various doses.…”

“…Such defective antibody responses have been related to a broad variety of immune defects including complement dysregulation, T-cell impaired function and altered antigen presentation, in addition to B-cell deficiency. 8 , 9 , 27 , 36 , 37 Because of this, vaccination of CLL patients early after diagnosis, and particularly even at the MBL stage when better responses might be expected, 8 , 33 has been proposed as a potentially effective strategy to improve serological immune protection of CLL patients against the most common pathogens. Parallel analyses focused on the humoral immunity and immune responses other than just the evaluation of plasma antibody levels are required to fully understand the uniqueness of the immunodeficiency status of MBL hi and CLL patients.…”

Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

“…However, this may need to be complemented by a functional antibody assay as antibody titers alone may give a misleading sense of immune response, especially with more severe dysfunction of humoral immunity, as is seen as MGUS progresses to MM [80]. Therefore, an approach to take with patients with MGUS may be to identify those patients with deficient antibody responses to vaccine antigens such as non-conjugated and conjugated pneumococcal; tetanus, diphtheria, meningococcus, and Haemophilus influenzae B [81]. From the observations that the response to vaccination is negatively correlated with disease progression [73], vaccination early in the disease would be expected to elicit greater antibody responses compared to those administered during later stages of the disease.…”