**2.3 Prognostic communication in patients with hematologic malignancies— Case-based discussion**

Prognostic information has generally been better studied in patients with solid tumors. Patients with hematological malignancies faced uncertain illness trajectory, treatment choices associated with risk of severe toxicity, but also a persistent chance for cure from stem cell transplant or CAR T cell therapy for the select few eligible for such options [13, 14]. Targeted therapy and immunotherapy have dramatically improved outcomes for patients with hematological malignancies [15].

#### *2.3.1 Case #1: Multiple myeloma*

A healthy man presented at age 68 with new-onset mid back pain. Imaging showed a deformity at T8 arising from a lytic lesion, along with lesions in other bones. Bone marrow biopsy demonstrated 40% clonal plasma cells, with FISH showing translocation (11, 14). Treatment was initiated with bortezomib, lenalidomide, and dexamethasone. After 2 cycles he developed grade 2 peripheral neuropathy, and bortezomib was discontinued. After 5 additional cycles of lenalidomide and dexamethasone, the monoclonal protein dropped more than 90% relative to pre-treatment baseline, meeting criteria for a very good partial response. He then received an autologous stem cell transplant, which he tolerated without major complications. Post-transplant, the monoclonal protein was undetectable, and lenalidomide maintenance was initiated. After just over two years of maintenance therapy he began to complain of worsening back pain. Imaging showed enlargement of several bony lesions with a new compression deformity at L1. His performance status remained excellent.

This example illustrates a common clinical situation of symptomatic relapse of multiple myeloma after stem cell transplant. Prior to 2012, the options for such a

#### **Figure 1.**

*A. Representative axial and coronal cross sectionals pretreatment with Alk inhibitor. B. Representative axial and coronal cross sectionals posttreatment with Alk inhibitor demonstrating near complete response.*

patient would have been limited. In 2022, the array of options in the same clinical situation is broad. Pomalidomide, carfilzomib, and daratumumab are all widely used drugs offering high response rates, alone and in numerous combinations, and all have mild toxicity profiles. These drugs can be combined to make several lines of therapy, even in patients with less-than-optimal organ function and performance status. Even after a patient becomes refractory to these drugs, newer salvage options are available, including selinexor, belantamab mafodotin, and elotuzumab. Several investigational drugs are in advanced stages of development and will likely add more treatment options in the near future. CAR-T therapy is commercially available as of 2021, and offers very high response rates, while incurring high cost and complexity of treatment. Finally, the patient's 11;14 translocation makes him a candidate to receive venetoclax, which has shown activity in this subgroup. With access to these treatments, survival for five years or longer after a first relapse is becoming routine. However, the likelihood of achieving response and the duration of response tend to drop with each successive line of therapy. It is rare to exhaust all available lines of therapy, but the tradeoffs between burdens and benefits of treatment shift progressively though the course of disease.

#### *2.3.2 Case #2: Acute myeloid leukemia*

A 73-year-old woman with diabetes, hypertension, stage IV chronic kidney disease, and mild dementia presented with nausea, vomiting, and chest pain.

*Prognostic Communication in the Era of Targeted Therapy and Immunotherapy DOI: http://dx.doi.org/10.5772/intechopen.105144*

Laboratory tests on admission showed leukocytosis of 22,000/μL along with moderate anemia and thrombocytopenia. Bone marrow biopsy was diagnostic for acute myeloid leukemia (AML).

Management of AML in the elderly is a longstanding challenge as the benefits of intensive chemotherapy are outweighed by the risk of infections and other complications. Historically these patients were treated with lower-intensity cytotoxic regimens, which could prolong survival by a few months at best.

Hypomethylating agents (azacitidine and decitabine) in combination with the BCL-2 inhibitor venetoclax have transformed the care of the elderly AML patient giving them a median survival of 14.7 months [16]. Although the combination can be tolerated by frail elders, it is not free from toxicity. The patient described above, despite kidney disease, early dementia, and limited functional status, has no absolute contraindications to such treatment, though these factors may negatively affect tolerability. Deciding whether to start combination therapy, a single agent, or best supportive care is therefore a complex and individualized decision.

#### **2.4 Effect of the progress in cancer therapy on clinical practice**

These cases serve to illustrate the high level of complexity that exists from response to later lines of therapy, to associated toxicities, to anticipated quality of life on treatment. Targeted and immunotherapies are associated with both palliative benefits in terms of pain/symptom control and improved survival benefits compared to former cytotoxic chemotherapy options (**Table 1**). Additionally, these therapeutics are associated with fewer and less severe toxicities such that patients can remain on treatment for extended periods of time.

These factors in combination with the hope for durable responses have resulted in a shift in referral patterns for patients with advanced and metastatic disease. In a 2019 study, a trend toward fewer hospice referrals and increased subacute rehab referrals from inpatient oncology units was noted with nearly two-thirds of patients never receiving additional cancer therapy [27]. In another retrospective study of deceased patients who had received immunotherapy, two-thirds had received immunotherapy in the last 90 days of life [28]. Notably, patients who had received immunotherapy in the last 30 days of life received less than 3 doses, had a poor performance status, had lower hospice enrollment, and higher rates of dying in the hospital [28]. Although extraordinary and durable responses are seen, these two studies emphasis the prognostic dilemma, as the majority of patients are likely to follow a different natural course. Therefore, assessing patient preferences for information sharing and goals of care is essential.

## **3. Prognostic communication preferences in oncology**

#### **3.1 Prognostic communication clinician factors**

Communication is a specialized skill. Indeed a review of the literature of prognosis related communication in advanced cancer patients suggests that it is useful to divide oncologists into three groups with respect to their ability to engage in meaningful highquality communication with their patients: Highly skilled oncologists need organizational support and can serve as mentors; moderately skilled oncologists may benefit from


#### **Table 1.**

*Evolution of prognosis in representative case examples.*

targeted skills training; and lower skilled oncologists may benefit from pairing with high level communicators or utilization of supportive programs to facilitate effective communication [8]. Discussing prognosis does include asking patients if they wish to receive this information and being prepared to respect their decision and re-engage periodically.

#### *Prognostic Communication in the Era of Targeted Therapy and Immunotherapy DOI: http://dx.doi.org/10.5772/intechopen.105144*

Communication training and skills are common barriers reported by clinicians. Inadequate training can result in brief, vague, or total avoidance of prognostic discussions. Conversely, physicians may use jargoned language with the intent to deliver accurate information or the uncertainty of prognosis, however no additional clarity is provided to the patient. Additionally, these conversations may be viewed as time consuming in the context of a busy oncology practice.

The emotional nature of prognosis contributes to additional clinician discomfort with delivering bad news and managing patient responses. Despite data suggesting otherwise, many physicians feel prognostic conversations decrease patient hope and create a less favorable provider-patient relationship [8, 29]. This poses a significant barrier as many oncologists develop a personal bond with their patients.

Finally, physician experience plays a significant role. Rapid progress in treatment has led to the finding that hematologic oncologists with fewer years of practice are less likely to engage in prognostic discussion [30] compared with younger physicians caring for patients with solid tumors who were significantly more likely to discuss prognosis than their older colleagues [31]. This reflects a higher level of "information uncertainty" and less confidence among junior hematologic oncologists as a major prognostication challenge for hematological malignancies [30].

#### **3.2 Prognostic communication patient preferences**

For patients and families, having prognostic information influences treatment preferences, decreases uncertainty and helps them to plan ahead for both personal and healthcare matters [32]. The majority of patients prefer to have prognosis communicated and nearly universally, they want accurate and honest information [33]. While some variation in preferences is influenced by age and sex, underlying cancer type and treatment goals do not impact patient preference [29]. In this era then, communication of prognosis with the elderly person with advanced cancer deserves special mention: Communicating prognosis in the elderly, especially in the very elderly (>85), or frail elderly is important for establishing patient centered goals of care and advance care planning. Fear, grief, and anxiety are common factors contributing to patient related barriers in prognostic communication and therefore invoking a patient's preference for information sharing remains essential [29]. Additionally, language and education barriers contribute to prognostic misunderstandings [29].
